pmid
stringlengths 5
8
| title
stringlengths 17
342
| abstract
stringlengths 1
4.53k
| revised_title
stringlengths 17
354
| revised_abstract
stringlengths 1
4.63k
| all_entity_list
listlengths 2
73
| head_gene_entity
dict | tail_diease_entity
dict | label
stringclasses 2
values |
|---|---|---|---|---|---|---|---|---|
10022417
|
The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.
|
Detailed endocrinological studies were performed in the three affected kindred of a family carrying mutations of the GnRH receptor gene. All three were compound heterozygotes carrying on one allele the Arg262Gln mutation and on the other allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas the Arg262Gln mutation altered activation of phospholipase C. The propositus, a 30-yr-old man, displayed complete idiopathic hypogonadotropic hypogonadism with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist (triptorelin), and absence of effect of pulsatile administration of GnRH. The two sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only partial idiopathic hypogonadotropic hypogonadism. They both had primary amenorrhea, and the younger sister displayed retarded bone maturation and uterus development, but both sisters had normal breast development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GnRH. In the two sisters, there were no spontaneous pulses of LH, but pulsatile administration of GnRH provoked a pulsatile secretion of LH in the younger sister. The same mutations of the GnRH receptor gene may thus determine different degrees of alteration of gonadotropin function in affected kindred of the same family.
|
The same molecular defects of the /"gonadotropin-releasing hormone receptor"/ determine a variable degree of hypogonadism in affected kindred.
|
Detailed endocrinological studies were performed in the three affected kindred of a family carrying mutations of the /"GnRH receptor"/ gene. All three were compound heterozygotes carrying on one allele the Arg262Gln mutation and on the other allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas the Arg262Gln mutation altered activation of phospholipase C. The propositus, a 30-yr-old man, displayed /"complete idiopathic hypogonadotropic hypogonadism"/ with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist (triptorelin), and absence of effect of pulsatile administration of GnRH. The two sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only partial /"idiopathic hypogonadotropic hypogonadism"/. They both had primary amenorrhea, and the younger sister displayed retarded bone maturation and uterus development, but both sisters had normal breast development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GnRH. In the two sisters, there were no spontaneous pulses of LH, but pulsatile administration of GnRH provoked a pulsatile secretion of LH in the younger sister. The same mutations of the /"GnRH receptor"/ gene may thus determine different degrees of alteration of gonadotropin function in affected kindred of the same family.
|
[
{
"begin_idx": "640",
"end_idx": "689",
"entity_id": "C562785",
"entity_type": "Disease",
"text_name": "complete idiopathic hypogonadotropic hypogonadism"
},
{
"begin_idx": "1013",
"end_idx": "1053",
"entity_id": "C562785",
"entity_type": "Disease",
"text_name": "idiopathic hypogonadotropic hypogonadism"
},
{
"begin_idx": "1077",
"end_idx": "1087",
"entity_id": "D000568",
"entity_type": "Disease",
"text_name": "amenorrhea"
},
{
"begin_idx": "105",
"end_idx": "117",
"entity_id": "D007006",
"entity_type": "Disease",
"text_name": "hypogonadism"
},
{
"begin_idx": "34",
"end_idx": "73",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "gonadotropin-releasing hormone receptor"
},
{
"begin_idx": "256",
"end_idx": "269",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "GnRH receptor"
},
{
"begin_idx": "1530",
"end_idx": "1543",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "GnRH receptor"
}
] |
{
"begin_idx": "34",
"end_idx": "73",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "gonadotropin-releasing hormone receptor"
}
|
{
"begin_idx": "640",
"end_idx": "689",
"entity_id": "C562785",
"entity_type": "Disease",
"text_name": "complete idiopathic hypogonadotropic hypogonadism"
}
|
Yes
|
10022417
|
The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.
|
Detailed endocrinological studies were performed in the three affected kindred of a family carrying mutations of the GnRH receptor gene. All three were compound heterozygotes carrying on one allele the Arg262Gln mutation and on the other allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas the Arg262Gln mutation altered activation of phospholipase C. The propositus, a 30-yr-old man, displayed complete idiopathic hypogonadotropic hypogonadism with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist (triptorelin), and absence of effect of pulsatile administration of GnRH. The two sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only partial idiopathic hypogonadotropic hypogonadism. They both had primary amenorrhea, and the younger sister displayed retarded bone maturation and uterus development, but both sisters had normal breast development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GnRH. In the two sisters, there were no spontaneous pulses of LH, but pulsatile administration of GnRH provoked a pulsatile secretion of LH in the younger sister. The same mutations of the GnRH receptor gene may thus determine different degrees of alteration of gonadotropin function in affected kindred of the same family.
|
The same molecular defects of the /"gonadotropin-releasing hormone receptor"/ determine a variable degree of /"hypogonadism"/ in affected kindred.
|
Detailed endocrinological studies were performed in the three affected kindred of a family carrying mutations of the /"GnRH receptor"/ gene. All three were compound heterozygotes carrying on one allele the Arg262Gln mutation and on the other allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas the Arg262Gln mutation altered activation of phospholipase C. The propositus, a 30-yr-old man, displayed complete idiopathic hypogonadotropic hypogonadism with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist (triptorelin), and absence of effect of pulsatile administration of GnRH. The two sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only partial idiopathic hypogonadotropic hypogonadism. They both had primary amenorrhea, and the younger sister displayed retarded bone maturation and uterus development, but both sisters had normal breast development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GnRH. In the two sisters, there were no spontaneous pulses of LH, but pulsatile administration of GnRH provoked a pulsatile secretion of LH in the younger sister. The same mutations of the /"GnRH receptor"/ gene may thus determine different degrees of alteration of gonadotropin function in affected kindred of the same family.
|
[
{
"begin_idx": "640",
"end_idx": "689",
"entity_id": "C562785",
"entity_type": "Disease",
"text_name": "complete idiopathic hypogonadotropic hypogonadism"
},
{
"begin_idx": "1013",
"end_idx": "1053",
"entity_id": "C562785",
"entity_type": "Disease",
"text_name": "idiopathic hypogonadotropic hypogonadism"
},
{
"begin_idx": "1077",
"end_idx": "1087",
"entity_id": "D000568",
"entity_type": "Disease",
"text_name": "amenorrhea"
},
{
"begin_idx": "105",
"end_idx": "117",
"entity_id": "D007006",
"entity_type": "Disease",
"text_name": "hypogonadism"
},
{
"begin_idx": "34",
"end_idx": "73",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "gonadotropin-releasing hormone receptor"
},
{
"begin_idx": "256",
"end_idx": "269",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "GnRH receptor"
},
{
"begin_idx": "1530",
"end_idx": "1543",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "GnRH receptor"
}
] |
{
"begin_idx": "1530",
"end_idx": "1543",
"entity_id": "2798",
"entity_type": "Gene",
"text_name": "GnRH receptor"
}
|
{
"begin_idx": "105",
"end_idx": "117",
"entity_id": "D007006",
"entity_type": "Disease",
"text_name": "hypogonadism"
}
|
No
|
10022458
|
Discordant measures of androgen-binding kinetics in two mutant androgen receptors causing mild or partial androgen insensitivity, respectively.
|
We have characterized two different mutations of the human androgen receptor (hAR) found in two unrelated subjects with androgen insensitivity syndrome (AIS): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS). Single base substitutions have been found in both individuals: E772A in the PAIS subject, and R871G in the MAIS patient. In COS-1 cells transfected with the E772A and R871G hARs, the apparent equilibrium dissociation constants (Kd) for mibolerone (MB) and methyltrienolone are normal. Nonetheless, the mutant hAR from the PAIS subject (E772A) has elevated nonequilibrium dissociation rate constants (k(diss)) for both androgens. In contrast, the MAIS subject's hAR (R871G) has k(diss) values that are apparently normal for MB and methyltrienolone; in addition, the R871G hAR's ability to bind MB resists thermal stress better than the hAR from the PAIS subject. The E772A and R871G hARs, therefore, confer the same pattern of discordant androgen-binding parameters in transfected COS-1 cells as observed previously in the subjects' genital skin fibroblasts. This proves their pathogenicity and correlates with the relative severity of the clinical phenotype. In COS-1 cells transfected with an androgen-responsive reporter gene, trans-activation was 50% of normal in cells containing either mutant hAR. However, mutant hAR-MB binding is unstable during prolonged incubation with MB, whereas normal hAR-MB binding increases. Thus, normal equilibrium dissociation constants alone, as determined by Scatchard analysis, may not be indicative of normal hAR function. An increased k(diss) despite a normal Kd for a given androgen suggests that it not only has increased egress from a mutant ligand-binding pocket, but also increased access to it. This hypothesis has certain implications in terms of the three-dimensional model of the ligand-binding domain of the nuclear receptor superfamily.
|
Discordant measures of androgen-binding kinetics in two mutant androgen receptors causing mild or partial androgen insensitivity, respectively.
|
We have characterized two different mutations of the human /"androgen receptor"/ (hAR) found in two unrelated subjects with /"androgen insensitivity syndrome"/ (/"AIS"/): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS). Single base substitutions have been found in both individuals: E772A in the PAIS subject, and R871G in the MAIS patient. In COS-1 cells transfected with the E772A and R871G hARs, the apparent equilibrium dissociation constants (Kd) for mibolerone (MB) and methyltrienolone are normal. Nonetheless, the mutant hAR from the PAIS subject (E772A) has elevated nonequilibrium dissociation rate constants (k(diss)) for both androgens. In contrast, the MAIS subject's hAR (R871G) has k(diss) values that are apparently normal for MB and methyltrienolone; in addition, the R871G hAR's ability to bind MB resists thermal stress better than the hAR from the PAIS subject. The E772A and R871G hARs, therefore, confer the same pattern of discordant androgen-binding parameters in transfected COS-1 cells as observed previously in the subjects' genital skin fibroblasts. This proves their pathogenicity and correlates with the relative severity of the clinical phenotype. In COS-1 cells transfected with an androgen-responsive reporter gene, trans-activation was 50% of normal in cells containing either mutant hAR. However, mutant hAR-MB binding is unstable during prolonged incubation with MB, whereas normal hAR-MB binding increases. Thus, normal equilibrium dissociation constants alone, as determined by Scatchard analysis, may not be indicative of normal hAR function. An increased k(diss) despite a normal Kd for a given androgen suggests that it not only has increased egress from a mutant ligand-binding pocket, but also increased access to it. This hypothesis has certain implications in terms of the three-dimensional model of the ligand-binding domain of the nuclear receptor superfamily.
|
[
{
"begin_idx": "264",
"end_idx": "295",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "androgen insensitivity syndrome"
},
{
"begin_idx": "297",
"end_idx": "300",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "AIS"
},
{
"begin_idx": "222",
"end_idx": "225",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "729",
"end_idx": "732",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "881",
"end_idx": "884",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "991",
"end_idx": "994",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1055",
"end_idx": "1058",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1518",
"end_idx": "1521",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1539",
"end_idx": "1542",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1618",
"end_idx": "1621",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1768",
"end_idx": "1771",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "203",
"end_idx": "220",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "androgen receptor"
},
{
"begin_idx": "593",
"end_idx": "597",
"entity_id": "6012",
"entity_type": "Gene",
"text_name": "hARs"
},
{
"begin_idx": "1102",
"end_idx": "1106",
"entity_id": "6012",
"entity_type": "Gene",
"text_name": "hARs"
}
] |
{
"begin_idx": "203",
"end_idx": "220",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "androgen receptor"
}
|
{
"begin_idx": "264",
"end_idx": "295",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "androgen insensitivity syndrome"
}
|
Yes
|
10022458
|
Discordant measures of androgen-binding kinetics in two mutant androgen receptors causing mild or partial androgen insensitivity, respectively.
|
We have characterized two different mutations of the human androgen receptor (hAR) found in two unrelated subjects with androgen insensitivity syndrome (AIS): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS). Single base substitutions have been found in both individuals: E772A in the PAIS subject, and R871G in the MAIS patient. In COS-1 cells transfected with the E772A and R871G hARs, the apparent equilibrium dissociation constants (Kd) for mibolerone (MB) and methyltrienolone are normal. Nonetheless, the mutant hAR from the PAIS subject (E772A) has elevated nonequilibrium dissociation rate constants (k(diss)) for both androgens. In contrast, the MAIS subject's hAR (R871G) has k(diss) values that are apparently normal for MB and methyltrienolone; in addition, the R871G hAR's ability to bind MB resists thermal stress better than the hAR from the PAIS subject. The E772A and R871G hARs, therefore, confer the same pattern of discordant androgen-binding parameters in transfected COS-1 cells as observed previously in the subjects' genital skin fibroblasts. This proves their pathogenicity and correlates with the relative severity of the clinical phenotype. In COS-1 cells transfected with an androgen-responsive reporter gene, trans-activation was 50% of normal in cells containing either mutant hAR. However, mutant hAR-MB binding is unstable during prolonged incubation with MB, whereas normal hAR-MB binding increases. Thus, normal equilibrium dissociation constants alone, as determined by Scatchard analysis, may not be indicative of normal hAR function. An increased k(diss) despite a normal Kd for a given androgen suggests that it not only has increased egress from a mutant ligand-binding pocket, but also increased access to it. This hypothesis has certain implications in terms of the three-dimensional model of the ligand-binding domain of the nuclear receptor superfamily.
|
Discordant measures of androgen-binding kinetics in two mutant androgen receptors causing mild or partial androgen insensitivity, respectively.
|
We have characterized two different mutations of the human androgen receptor (/"hAR"/) found in two unrelated subjects with /"androgen insensitivity syndrome"/ (/"AIS"/): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS). Single base substitutions have been found in both individuals: E772A in the PAIS subject, and R871G in the MAIS patient. In COS-1 cells transfected with the E772A and R871G hARs, the apparent equilibrium dissociation constants (Kd) for mibolerone (MB) and methyltrienolone are normal. Nonetheless, the mutant /"hAR"/ from the PAIS subject (E772A) has elevated nonequilibrium dissociation rate constants (k(diss)) for both androgens. In contrast, the MAIS subject's /"hAR"/ (R871G) has k(diss) values that are apparently normal for MB and methyltrienolone; in addition, the R871G /"hAR"/'s ability to bind MB resists thermal stress better than the /"hAR"/ from the PAIS subject. The E772A and R871G hARs, therefore, confer the same pattern of discordant androgen-binding parameters in transfected COS-1 cells as observed previously in the subjects' genital skin fibroblasts. This proves their pathogenicity and correlates with the relative severity of the clinical phenotype. In COS-1 cells transfected with an androgen-responsive reporter gene, trans-activation was 50% of normal in cells containing either mutant /"hAR"/. However, mutant /"hAR"/-MB binding is unstable during prolonged incubation with MB, whereas normal /"hAR"/-MB binding increases. Thus, normal equilibrium dissociation constants alone, as determined by Scatchard analysis, may not be indicative of normal /"hAR"/ function. An increased k(diss) despite a normal Kd for a given androgen suggests that it not only has increased egress from a mutant ligand-binding pocket, but also increased access to it. This hypothesis has certain implications in terms of the three-dimensional model of the ligand-binding domain of the nuclear receptor superfamily.
|
[
{
"begin_idx": "264",
"end_idx": "295",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "androgen insensitivity syndrome"
},
{
"begin_idx": "297",
"end_idx": "300",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "AIS"
},
{
"begin_idx": "222",
"end_idx": "225",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "729",
"end_idx": "732",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "881",
"end_idx": "884",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "991",
"end_idx": "994",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1055",
"end_idx": "1058",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1518",
"end_idx": "1521",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1539",
"end_idx": "1542",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1618",
"end_idx": "1621",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "1768",
"end_idx": "1771",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
},
{
"begin_idx": "203",
"end_idx": "220",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "androgen receptor"
},
{
"begin_idx": "593",
"end_idx": "597",
"entity_id": "6012",
"entity_type": "Gene",
"text_name": "hARs"
},
{
"begin_idx": "1102",
"end_idx": "1106",
"entity_id": "6012",
"entity_type": "Gene",
"text_name": "hARs"
}
] |
{
"begin_idx": "1768",
"end_idx": "1771",
"entity_id": "10894",
"entity_type": "Gene",
"text_name": "hAR"
}
|
{
"begin_idx": "264",
"end_idx": "295",
"entity_id": "D013734",
"entity_type": "Disease",
"text_name": "androgen insensitivity syndrome"
}
|
No
|
10022756
|
The *NAT2 slow acetylator genotype is associated with bladder cancer in Taiwanese, but not in the Black Foot Disease endemic area population.
|
The /"NAT2"/2 slow acetylator genotype is associated with /"bladder cancer"/ in Taiwanese, but not in the Black Foot Disease endemic area population.
|
[
{
"begin_idx": "54",
"end_idx": "68",
"entity_id": "D001749",
"entity_type": "Disease",
"text_name": "bladder cancer"
},
{
"begin_idx": "104",
"end_idx": "116",
"entity_id": "D005534",
"entity_type": "Disease",
"text_name": "Foot Disease"
},
{
"begin_idx": "4",
"end_idx": "8",
"entity_id": "10",
"entity_type": "Gene",
"text_name": "NAT2"
}
] |
{
"begin_idx": "4",
"end_idx": "8",
"entity_id": "10",
"entity_type": "Gene",
"text_name": "NAT2"
}
|
{
"begin_idx": "54",
"end_idx": "68",
"entity_id": "D001749",
"entity_type": "Disease",
"text_name": "bladder cancer"
}
|
Yes
|
||
10022756
|
The *NAT2 slow acetylator genotype is associated with bladder cancer in Taiwanese, but not in the Black Foot Disease endemic area population.
|
The /"NAT2"/2 slow acetylator genotype is associated with bladder cancer in Taiwanese, but not in the Black /"Foot Disease"/ endemic area population.
|
[
{
"begin_idx": "54",
"end_idx": "68",
"entity_id": "D001749",
"entity_type": "Disease",
"text_name": "bladder cancer"
},
{
"begin_idx": "104",
"end_idx": "116",
"entity_id": "D005534",
"entity_type": "Disease",
"text_name": "Foot Disease"
},
{
"begin_idx": "4",
"end_idx": "8",
"entity_id": "10",
"entity_type": "Gene",
"text_name": "NAT2"
}
] |
{
"begin_idx": "4",
"end_idx": "8",
"entity_id": "10",
"entity_type": "Gene",
"text_name": "NAT2"
}
|
{
"begin_idx": "104",
"end_idx": "116",
"entity_id": "D005534",
"entity_type": "Disease",
"text_name": "Foot Disease"
}
|
No
|
||
10024302
|
Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.
|
The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.
|
Genomic organization of the /"KCNQ1"/ K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.
|
The voltage-gated K+ channel /"KVLQT1"/ is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human /"KCNQ1"/ gene encoding the alpha subunit of the /"KVLQT1"/ channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the /"Romano-Ward syndrome"/, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of /"KCNQ1"/, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete /"KCNQ1"/ gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of /"KCNQ1"/: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.
|
[
{
"begin_idx": "521",
"end_idx": "544",
"entity_id": "D001145",
"entity_type": "Disease",
"text_name": "ventricular arrhythmias"
},
{
"begin_idx": "648",
"end_idx": "666",
"entity_id": "D003638",
"entity_type": "Disease",
"text_name": "bilateral deafness"
},
{
"begin_idx": "550",
"end_idx": "562",
"entity_id": "D003645",
"entity_type": "Disease",
"text_name": "sudden death"
},
{
"begin_idx": "423",
"end_idx": "438",
"entity_id": "D006331",
"entity_type": "Disease",
"text_name": "cardiac disease"
},
{
"begin_idx": "100",
"end_idx": "116",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "long-QT syndrome"
},
{
"begin_idx": "362",
"end_idx": "378",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "long-QT syndrome"
},
{
"begin_idx": "380",
"end_idx": "384",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "1219",
"end_idx": "1223",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "1620",
"end_idx": "1624",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "610",
"end_idx": "632",
"entity_id": "D029593",
"entity_type": "Disease",
"text_name": "Lange-Nielsen syndrome"
},
{
"begin_idx": "444",
"end_idx": "464",
"entity_id": "D029597",
"entity_type": "Disease",
"text_name": "Romano-Ward syndrome"
},
{
"begin_idx": "122",
"end_idx": "146",
"entity_id": "3752",
"entity_type": "Gene",
"text_name": "voltage-gated K+ channel"
},
{
"begin_idx": "28",
"end_idx": "33",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "147",
"end_idx": "153",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KVLQT1"
},
{
"begin_idx": "292",
"end_idx": "297",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "337",
"end_idx": "343",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KVLQT1"
},
{
"begin_idx": "732",
"end_idx": "737",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "1144",
"end_idx": "1149",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "1324",
"end_idx": "1329",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
}
] |
{
"begin_idx": "147",
"end_idx": "153",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KVLQT1"
}
|
{
"begin_idx": "444",
"end_idx": "464",
"entity_id": "D029597",
"entity_type": "Disease",
"text_name": "Romano-Ward syndrome"
}
|
Yes
|
10024302
|
Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.
|
The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.
|
Genomic organization of the /"KCNQ1"/ K+ channel gene and identification of C-terminal mutations in the /"long-QT syndrome"/.
|
The voltage-gated K+ channel /"KVLQT1"/ is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human /"KCNQ1"/ gene encoding the alpha subunit of the /"KVLQT1"/ channel cause the /"long-QT syndrome"/ (/"LQTS"/). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of /"KCNQ1"/, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete /"KCNQ1"/ gene. By use of these tools, five novel mutations were identified in /"LQTS"/ patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of /"KCNQ1"/: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large /"LQTS"/ cohorts.
|
[
{
"begin_idx": "521",
"end_idx": "544",
"entity_id": "D001145",
"entity_type": "Disease",
"text_name": "ventricular arrhythmias"
},
{
"begin_idx": "648",
"end_idx": "666",
"entity_id": "D003638",
"entity_type": "Disease",
"text_name": "bilateral deafness"
},
{
"begin_idx": "550",
"end_idx": "562",
"entity_id": "D003645",
"entity_type": "Disease",
"text_name": "sudden death"
},
{
"begin_idx": "423",
"end_idx": "438",
"entity_id": "D006331",
"entity_type": "Disease",
"text_name": "cardiac disease"
},
{
"begin_idx": "100",
"end_idx": "116",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "long-QT syndrome"
},
{
"begin_idx": "362",
"end_idx": "378",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "long-QT syndrome"
},
{
"begin_idx": "380",
"end_idx": "384",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "1219",
"end_idx": "1223",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "1620",
"end_idx": "1624",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "LQTS"
},
{
"begin_idx": "610",
"end_idx": "632",
"entity_id": "D029593",
"entity_type": "Disease",
"text_name": "Lange-Nielsen syndrome"
},
{
"begin_idx": "444",
"end_idx": "464",
"entity_id": "D029597",
"entity_type": "Disease",
"text_name": "Romano-Ward syndrome"
},
{
"begin_idx": "122",
"end_idx": "146",
"entity_id": "3752",
"entity_type": "Gene",
"text_name": "voltage-gated K+ channel"
},
{
"begin_idx": "28",
"end_idx": "33",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "147",
"end_idx": "153",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KVLQT1"
},
{
"begin_idx": "292",
"end_idx": "297",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "337",
"end_idx": "343",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KVLQT1"
},
{
"begin_idx": "732",
"end_idx": "737",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "1144",
"end_idx": "1149",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
},
{
"begin_idx": "1324",
"end_idx": "1329",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
}
] |
{
"begin_idx": "732",
"end_idx": "737",
"entity_id": "3784",
"entity_type": "Gene",
"text_name": "KCNQ1"
}
|
{
"begin_idx": "100",
"end_idx": "116",
"entity_id": "D008133",
"entity_type": "Disease",
"text_name": "long-QT syndrome"
}
|
No
|
10025794
|
Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS.
|
OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of MS. BACKGROUND: Genetic susceptibility to MS is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for MS susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite MS and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA/IL-1beta combination was associated with disease severity. MS patients with the IL-1RA allele 2+/IL-1beta allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: IL-1RA and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.
|
Association of /"interleukin-1beta"/ and interleukin-1 receptor antagonist genes with disease severity in /"MS"/.
|
OBJECTIVE: To investigate whether polymorphisms in the /"interleukin (IL)-1beta"/ and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of /"MS"/. BACKGROUND: Genetic susceptibility to /"MS"/ is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for /"MS"/ susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite /"MS"/ and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between /"MS"/ patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA//"IL-1beta"/ combination was associated with disease severity. /"MS"/ patients with the IL-1RA allele 2+//"IL-1beta"/ allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: IL-1RA and /"IL-1beta"/ are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.
|
[
{
"begin_idx": "102",
"end_idx": "104",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "303",
"end_idx": "305",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "345",
"end_idx": "347",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "462",
"end_idx": "464",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "573",
"end_idx": "575",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "886",
"end_idx": "888",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "1178",
"end_idx": "1180",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "15",
"end_idx": "32",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin-1beta"
},
{
"begin_idx": "161",
"end_idx": "183",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin (IL)-1beta"
},
{
"begin_idx": "1119",
"end_idx": "1127",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "1216",
"end_idx": "1224",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "1408",
"end_idx": "1416",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "188",
"end_idx": "212",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1 receptor antagonist"
},
{
"begin_idx": "214",
"end_idx": "220",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1112",
"end_idx": "1118",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1199",
"end_idx": "1205",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1397",
"end_idx": "1403",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
}
] |
{
"begin_idx": "161",
"end_idx": "183",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin (IL)-1beta"
}
|
{
"begin_idx": "102",
"end_idx": "104",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
}
|
Yes
|
10025794
|
Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS.
|
OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of MS. BACKGROUND: Genetic susceptibility to MS is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for MS susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite MS and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA/IL-1beta combination was associated with disease severity. MS patients with the IL-1RA allele 2+/IL-1beta allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: IL-1RA and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.
|
Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in /"MS"/.
|
OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1beta and /"IL-1 receptor antagonist"/ (/"IL-1RA"/) genes are associated with both susceptibility to and clinical characteristics of /"MS"/. BACKGROUND: Genetic susceptibility to /"MS"/ is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for /"MS"/ susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite /"MS"/ and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between /"MS"/ patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific /"IL-1RA"//IL-1beta combination was associated with disease severity. /"MS"/ patients with the /"IL-1RA"/ allele 2+/IL-1beta allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: /"IL-1RA"/ and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.
|
[
{
"begin_idx": "102",
"end_idx": "104",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "303",
"end_idx": "305",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "345",
"end_idx": "347",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "462",
"end_idx": "464",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "573",
"end_idx": "575",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "886",
"end_idx": "888",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "1178",
"end_idx": "1180",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
},
{
"begin_idx": "15",
"end_idx": "32",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin-1beta"
},
{
"begin_idx": "161",
"end_idx": "183",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin (IL)-1beta"
},
{
"begin_idx": "1119",
"end_idx": "1127",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "1216",
"end_idx": "1224",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "1408",
"end_idx": "1416",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "IL-1beta"
},
{
"begin_idx": "188",
"end_idx": "212",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1 receptor antagonist"
},
{
"begin_idx": "214",
"end_idx": "220",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1112",
"end_idx": "1118",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1199",
"end_idx": "1205",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
},
{
"begin_idx": "1397",
"end_idx": "1403",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1RA"
}
] |
{
"begin_idx": "188",
"end_idx": "212",
"entity_id": "3557",
"entity_type": "Gene",
"text_name": "IL-1 receptor antagonist"
}
|
{
"begin_idx": "102",
"end_idx": "104",
"entity_id": "D009103",
"entity_type": "Disease",
"text_name": "MS"
}
|
Yes
|
10027593
|
UKPDS 31: Hepatocyte nuclear factor-1alpha (the MODY3 gene) mutations in late onset Type II diabetic patients in the United Kingdom. United Kingdom prospective diabetes study.
|
UKPDS 31: Hepatocyte nuclear factor-1alpha (the /"MODY3"/ gene) mutations in late onset /"Type II diabetic"/ patients in the United Kingdom. United Kingdom prospective diabetes study.
|
[
{
"begin_idx": "160",
"end_idx": "168",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "84",
"end_idx": "100",
"entity_id": "D003924",
"entity_type": "Disease",
"text_name": "Type II diabetic"
},
{
"begin_idx": "48",
"end_idx": "53",
"entity_id": "6927",
"entity_type": "Gene",
"text_name": "MODY3"
}
] |
{
"begin_idx": "48",
"end_idx": "53",
"entity_id": "6927",
"entity_type": "Gene",
"text_name": "MODY3"
}
|
{
"begin_idx": "84",
"end_idx": "100",
"entity_id": "D003924",
"entity_type": "Disease",
"text_name": "Type II diabetic"
}
|
Yes
|
||
10027593
|
UKPDS 31: Hepatocyte nuclear factor-1alpha (the MODY3 gene) mutations in late onset Type II diabetic patients in the United Kingdom. United Kingdom prospective diabetes study.
|
UKPDS 31: Hepatocyte nuclear factor-1alpha (the /"MODY3"/ gene) mutations in late onset Type II diabetic patients in the United Kingdom. United Kingdom prospective /"diabetes"/ study.
|
[
{
"begin_idx": "160",
"end_idx": "168",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "84",
"end_idx": "100",
"entity_id": "D003924",
"entity_type": "Disease",
"text_name": "Type II diabetic"
},
{
"begin_idx": "48",
"end_idx": "53",
"entity_id": "6927",
"entity_type": "Gene",
"text_name": "MODY3"
}
] |
{
"begin_idx": "48",
"end_idx": "53",
"entity_id": "6927",
"entity_type": "Gene",
"text_name": "MODY3"
}
|
{
"begin_idx": "160",
"end_idx": "168",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
}
|
No
|
||
10027710
|
Identification of a novel mutation in a non-Jewish factor XI deficient kindred.
|
The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (FXI activity 1.6 U/dl). A sensitive ELISA failed to detect FXI antigen in the propositus. Sequence analysis of the entire FXI gene revealed a TGG to TGC transversion in codon 228 of exon 7 (FXI-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of FXI. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding tendency but it may correlate with a FXI-like antigen and factor IX binding activity expressed on platelets.
|
Identification of a novel mutation in a non-Jewish /"factor XI deficient"/ kindred.
|
The role of /"factor XI"/ (/"FXI"/) in blood coagulation has been clarified in recent years by descriptions of /"FXI-deficient"/ patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an /"Italian FXI-deficient"/ patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (/"FXI"/ activity 1.6 U/dl). A sensitive ELISA failed to detect /"FXI"/ antigen in the propositus. Sequence analysis of the entire /"FXI"/ gene revealed a TGG to TGC transversion in codon 228 of exon 7 (/"FXI"/-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of /"FXI"/. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of /"FXI"/ and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding tendency but it may correlate with a /"FXI"/-like antigen and factor IX binding activity expressed on platelets.
|
[
{
"begin_idx": "111",
"end_idx": "128",
"entity_id": "D001778",
"entity_type": "Disease",
"text_name": "blood coagulation"
},
{
"begin_idx": "51",
"end_idx": "70",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "factor XI deficient"
},
{
"begin_idx": "183",
"end_idx": "196",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "FXI-deficient"
},
{
"begin_idx": "309",
"end_idx": "330",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "Italian FXI-deficient"
},
{
"begin_idx": "233",
"end_idx": "241",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "485",
"end_idx": "493",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "1092",
"end_idx": "1100",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "442",
"end_idx": "456",
"entity_id": "D013923",
"entity_type": "Disease",
"text_name": "thromboembolic"
},
{
"begin_idx": "998",
"end_idx": "1019",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "inherited abnormality"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "factor XI"
},
{
"begin_idx": "103",
"end_idx": "106",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "495",
"end_idx": "498",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "554",
"end_idx": "557",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "617",
"end_idx": "620",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "685",
"end_idx": "688",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "790",
"end_idx": "793",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "966",
"end_idx": "969",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "1138",
"end_idx": "1141",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
}
] |
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "factor XI"
}
|
{
"begin_idx": "309",
"end_idx": "330",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "Italian FXI-deficient"
}
|
Yes
|
10027710
|
Identification of a novel mutation in a non-Jewish factor XI deficient kindred.
|
The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (FXI activity 1.6 U/dl). A sensitive ELISA failed to detect FXI antigen in the propositus. Sequence analysis of the entire FXI gene revealed a TGG to TGC transversion in codon 228 of exon 7 (FXI-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of FXI. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding tendency but it may correlate with a FXI-like antigen and factor IX binding activity expressed on platelets.
|
Identification of a novel mutation in a non-Jewish factor XI deficient kindred.
|
The role of /"factor XI"/ (/"FXI"/) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive /"bleeding"/ after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of /"bleeding"/ (/"FXI"/ activity 1.6 U/dl). A sensitive ELISA failed to detect /"FXI"/ antigen in the propositus. Sequence analysis of the entire /"FXI"/ gene revealed a TGG to TGC transversion in codon 228 of exon 7 (/"FXI"/-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of /"FXI"/. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of /"FXI"/ and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a /"bleeding"/ tendency but it may correlate with a /"FXI"/-like antigen and factor IX binding activity expressed on platelets.
|
[
{
"begin_idx": "111",
"end_idx": "128",
"entity_id": "D001778",
"entity_type": "Disease",
"text_name": "blood coagulation"
},
{
"begin_idx": "51",
"end_idx": "70",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "factor XI deficient"
},
{
"begin_idx": "183",
"end_idx": "196",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "FXI-deficient"
},
{
"begin_idx": "309",
"end_idx": "330",
"entity_id": "D005173",
"entity_type": "Disease",
"text_name": "Italian FXI-deficient"
},
{
"begin_idx": "233",
"end_idx": "241",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "485",
"end_idx": "493",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "1092",
"end_idx": "1100",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
},
{
"begin_idx": "442",
"end_idx": "456",
"entity_id": "D013923",
"entity_type": "Disease",
"text_name": "thromboembolic"
},
{
"begin_idx": "998",
"end_idx": "1019",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "inherited abnormality"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "factor XI"
},
{
"begin_idx": "103",
"end_idx": "106",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "495",
"end_idx": "498",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "554",
"end_idx": "557",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "617",
"end_idx": "620",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "685",
"end_idx": "688",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "790",
"end_idx": "793",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "966",
"end_idx": "969",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
},
{
"begin_idx": "1138",
"end_idx": "1141",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
}
] |
{
"begin_idx": "617",
"end_idx": "620",
"entity_id": "2160",
"entity_type": "Gene",
"text_name": "FXI"
}
|
{
"begin_idx": "1092",
"end_idx": "1100",
"entity_id": "D006470",
"entity_type": "Disease",
"text_name": "bleeding"
}
|
No
|
10029606
|
Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.
|
X-linked sideroblastic anemia (XLSA) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo XLSA mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated XLSA hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two XLSA probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia.
|
Four new mutations in the erythroid-specific 5-aminolevulinate synthase (/"ALAS2"/) gene causing /"X-linked sideroblastic anemia"/: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.
|
/"X-linked sideroblastic anemia"/ (/"XLSA"/) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (/"ALAS2"/). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo /"XLSA"/ mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated /"XLSA"/ hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two /"XLSA"/ probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of /"XLSA"/ probands in order to prevent a downward spiral of iron toxicity and refractory anemia.
|
[
{
"begin_idx": "93",
"end_idx": "122",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "X-linked sideroblastic anemia"
},
{
"begin_idx": "254",
"end_idx": "283",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "X-linked sideroblastic anemia"
},
{
"begin_idx": "285",
"end_idx": "289",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "654",
"end_idx": "658",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "871",
"end_idx": "875",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1151",
"end_idx": "1155",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1592",
"end_idx": "1596",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1665",
"end_idx": "1682",
"entity_id": "D000740",
"entity_type": "Disease",
"text_name": "refractory anemia"
},
{
"begin_idx": "226",
"end_idx": "252",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "hereditary hemochromatosis"
},
{
"begin_idx": "799",
"end_idx": "825",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "hereditary hemochromatosis"
},
{
"begin_idx": "827",
"end_idx": "829",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "HH"
},
{
"begin_idx": "1079",
"end_idx": "1081",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "HH"
},
{
"begin_idx": "1647",
"end_idx": "1660",
"entity_id": "D064420",
"entity_type": "Disease",
"text_name": "iron toxicity"
},
{
"begin_idx": "73",
"end_idx": "78",
"entity_id": "212",
"entity_type": "Gene",
"text_name": "ALAS2"
},
{
"begin_idx": "415",
"end_idx": "420",
"entity_id": "212",
"entity_type": "Gene",
"text_name": "ALAS2"
},
{
"begin_idx": "831",
"end_idx": "834",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
},
{
"begin_idx": "964",
"end_idx": "967",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
}
] |
{
"begin_idx": "73",
"end_idx": "78",
"entity_id": "212",
"entity_type": "Gene",
"text_name": "ALAS2"
}
|
{
"begin_idx": "93",
"end_idx": "122",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "X-linked sideroblastic anemia"
}
|
Yes
|
10029606
|
Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.
|
X-linked sideroblastic anemia (XLSA) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo XLSA mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated XLSA hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two XLSA probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia.
|
Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing /"X-linked sideroblastic anemia"/: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.
|
/"X-linked sideroblastic anemia"/ (/"XLSA"/) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo /"XLSA"/ mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) /"HFE"/ mutant allele C282Y in 18 unrelated /"XLSA"/ hemizygotes than found in the normal population, indicating a role for coinheritance of /"HFE"/ alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two /"XLSA"/ probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of /"XLSA"/ probands in order to prevent a downward spiral of iron toxicity and refractory anemia.
|
[
{
"begin_idx": "93",
"end_idx": "122",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "X-linked sideroblastic anemia"
},
{
"begin_idx": "254",
"end_idx": "283",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "X-linked sideroblastic anemia"
},
{
"begin_idx": "285",
"end_idx": "289",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "654",
"end_idx": "658",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "871",
"end_idx": "875",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1151",
"end_idx": "1155",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1592",
"end_idx": "1596",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
},
{
"begin_idx": "1665",
"end_idx": "1682",
"entity_id": "D000740",
"entity_type": "Disease",
"text_name": "refractory anemia"
},
{
"begin_idx": "226",
"end_idx": "252",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "hereditary hemochromatosis"
},
{
"begin_idx": "799",
"end_idx": "825",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "hereditary hemochromatosis"
},
{
"begin_idx": "827",
"end_idx": "829",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "HH"
},
{
"begin_idx": "1079",
"end_idx": "1081",
"entity_id": "D006432",
"entity_type": "Disease",
"text_name": "HH"
},
{
"begin_idx": "1647",
"end_idx": "1660",
"entity_id": "D064420",
"entity_type": "Disease",
"text_name": "iron toxicity"
},
{
"begin_idx": "73",
"end_idx": "78",
"entity_id": "212",
"entity_type": "Gene",
"text_name": "ALAS2"
},
{
"begin_idx": "415",
"end_idx": "420",
"entity_id": "212",
"entity_type": "Gene",
"text_name": "ALAS2"
},
{
"begin_idx": "831",
"end_idx": "834",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
},
{
"begin_idx": "964",
"end_idx": "967",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
}
] |
{
"begin_idx": "831",
"end_idx": "834",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
}
|
{
"begin_idx": "871",
"end_idx": "875",
"entity_id": "C536761",
"entity_type": "Disease",
"text_name": "XLSA"
}
|
No
|
10036316
|
Maroteaux-lamy syndrome: five novel mutations and their structural localization.
|
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ASB). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation.
|
/"Maroteaux-lamy syndrome"/: five novel mutations and their structural localization.
|
/"Maroteaux-Lamy syndrome"/ (/"mucopolysaccharidosis type VI"/, /"MPS VI"/) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (/"arylsulfatase B"/, /"ASB"/). Mutation analysis in /"Maroteaux-Lamy syndrome"/ resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation.
|
[
{
"begin_idx": "0",
"end_idx": "23",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-lamy syndrome"
},
{
"begin_idx": "81",
"end_idx": "104",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-Lamy syndrome"
},
{
"begin_idx": "106",
"end_idx": "135",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "mucopolysaccharidosis type VI"
},
{
"begin_idx": "137",
"end_idx": "143",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "MPS VI"
},
{
"begin_idx": "305",
"end_idx": "328",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-Lamy syndrome"
},
{
"begin_idx": "151",
"end_idx": "179",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disorder"
},
{
"begin_idx": "582",
"end_idx": "622",
"entity_id": "D034721",
"entity_type": "Disease",
"text_name": "amplification refractory mutation system"
},
{
"begin_idx": "624",
"end_idx": "628",
"entity_id": "D034721",
"entity_type": "Disease",
"text_name": "ARMS"
},
{
"begin_idx": "261",
"end_idx": "276",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "arylsulfatase B"
},
{
"begin_idx": "278",
"end_idx": "281",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "ASB"
}
] |
{
"begin_idx": "261",
"end_idx": "276",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "arylsulfatase B"
}
|
{
"begin_idx": "106",
"end_idx": "135",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "mucopolysaccharidosis type VI"
}
|
Yes
|
10036316
|
Maroteaux-lamy syndrome: five novel mutations and their structural localization.
|
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ASB). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation.
|
Maroteaux-lamy syndrome: five novel mutations and their structural localization.
|
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an /"autosomal recessive disorder"/ due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (/"arylsulfatase B"/, /"ASB"/). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation.
|
[
{
"begin_idx": "0",
"end_idx": "23",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-lamy syndrome"
},
{
"begin_idx": "81",
"end_idx": "104",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-Lamy syndrome"
},
{
"begin_idx": "106",
"end_idx": "135",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "mucopolysaccharidosis type VI"
},
{
"begin_idx": "137",
"end_idx": "143",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "MPS VI"
},
{
"begin_idx": "305",
"end_idx": "328",
"entity_id": "D009087",
"entity_type": "Disease",
"text_name": "Maroteaux-Lamy syndrome"
},
{
"begin_idx": "151",
"end_idx": "179",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disorder"
},
{
"begin_idx": "582",
"end_idx": "622",
"entity_id": "D034721",
"entity_type": "Disease",
"text_name": "amplification refractory mutation system"
},
{
"begin_idx": "624",
"end_idx": "628",
"entity_id": "D034721",
"entity_type": "Disease",
"text_name": "ARMS"
},
{
"begin_idx": "261",
"end_idx": "276",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "arylsulfatase B"
},
{
"begin_idx": "278",
"end_idx": "281",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "ASB"
}
] |
{
"begin_idx": "278",
"end_idx": "281",
"entity_id": "411",
"entity_type": "Gene",
"text_name": "ASB"
}
|
{
"begin_idx": "151",
"end_idx": "179",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disorder"
}
|
No
|
10049523
|
An interluekin 1B allele, which correlates with a high secretor phenotype, is associated with diabetic nephropathy.
|
Induction of interleukin 1 activates vascular endothelial and kidney mesangial cells, and increases production of type IV (basement membrane) collagen. Hence, genes within the interleukin 1 gene cluster are potential candidates in the pathogenesis of diabetic nephropathy. In a previously validated case-control study from Northern Ireland, consisting of 95 patients with insulin-dependent (type 1) diabetes and nephropathy (cases) and 96 patients with insulin-dependent (type 1) diabetes without nephropathy (controls), the authors performed PCR-based genotyping of specific DNA polymorphisms within the interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor antagonist genes. The groups were matched for age at onset and duration of diabetes. A statistically significant increase was found in the allele frequency of the interleukin 1B*2 allele in cases compared to controls (chi2=7. 19, df.=1; P=0.007, Pcorr=0.028). The results of this study suggest that the interleukin 1B*2 allele, or a susceptibility factor in linkage disequilibrium with this allele, is associated with diabetic nephropathy in the Northern Ireland population.
|
An interluekin 1B allele, which correlates with a high secretor phenotype, is associated with /"diabetic nephropathy"/.
|
Induction of interleukin 1 activates vascular endothelial and kidney mesangial cells, and increases production of type IV (basement membrane) collagen. Hence, genes within the interleukin 1 gene cluster are potential candidates in the pathogenesis of /"diabetic nephropathy"/. In a previously validated case-control study from Northern Ireland, consisting of 95 patients with insulin-dependent (type 1) diabetes and nephropathy (cases) and 96 patients with insulin-dependent (type 1) diabetes without nephropathy (controls), the authors performed PCR-based genotyping of specific DNA polymorphisms within the /"interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"/ antagonist genes. The groups were matched for age at onset and duration of diabetes. A statistically significant increase was found in the allele frequency of the /"interleukin 1B"/*2 allele in cases compared to controls (chi2=7. 19, df.=1; P=0.007, Pcorr=0.028). The results of this study suggest that the /"interleukin 1B"/*2 allele, or a susceptibility factor in linkage disequilibrium with this allele, is associated with /"diabetic nephropathy"/ in the Northern Ireland population.
|
[
{
"begin_idx": "515",
"end_idx": "523",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "596",
"end_idx": "604",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "887",
"end_idx": "895",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "94",
"end_idx": "114",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "367",
"end_idx": "387",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "1230",
"end_idx": "1250",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "528",
"end_idx": "539",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "nephropathy"
},
{
"begin_idx": "613",
"end_idx": "624",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "nephropathy"
},
{
"begin_idx": "129",
"end_idx": "142",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1"
},
{
"begin_idx": "292",
"end_idx": "305",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1"
},
{
"begin_idx": "721",
"end_idx": "811",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"
},
{
"begin_idx": "721",
"end_idx": "811",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"
},
{
"begin_idx": "975",
"end_idx": "989",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1B"
},
{
"begin_idx": "1115",
"end_idx": "1129",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1B"
}
] |
{
"begin_idx": "721",
"end_idx": "811",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"
}
|
{
"begin_idx": "94",
"end_idx": "114",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
}
|
Yes
|
10049523
|
An interluekin 1B allele, which correlates with a high secretor phenotype, is associated with diabetic nephropathy.
|
Induction of interleukin 1 activates vascular endothelial and kidney mesangial cells, and increases production of type IV (basement membrane) collagen. Hence, genes within the interleukin 1 gene cluster are potential candidates in the pathogenesis of diabetic nephropathy. In a previously validated case-control study from Northern Ireland, consisting of 95 patients with insulin-dependent (type 1) diabetes and nephropathy (cases) and 96 patients with insulin-dependent (type 1) diabetes without nephropathy (controls), the authors performed PCR-based genotyping of specific DNA polymorphisms within the interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor antagonist genes. The groups were matched for age at onset and duration of diabetes. A statistically significant increase was found in the allele frequency of the interleukin 1B*2 allele in cases compared to controls (chi2=7. 19, df.=1; P=0.007, Pcorr=0.028). The results of this study suggest that the interleukin 1B*2 allele, or a susceptibility factor in linkage disequilibrium with this allele, is associated with diabetic nephropathy in the Northern Ireland population.
|
An interluekin 1B allele, which correlates with a high secretor phenotype, is associated with diabetic nephropathy.
|
Induction of /"interleukin 1"/ activates vascular endothelial and kidney mesangial cells, and increases production of type IV (basement membrane) collagen. Hence, genes within the /"interleukin 1"/ gene cluster are potential candidates in the pathogenesis of diabetic nephropathy. In a previously validated case-control study from Northern Ireland, consisting of 95 patients with insulin-dependent (type 1) /"diabetes"/ and nephropathy (cases) and 96 patients with insulin-dependent (type 1) /"diabetes"/ without nephropathy (controls), the authors performed PCR-based genotyping of specific DNA polymorphisms within the /"interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"/ antagonist genes. The groups were matched for age at onset and duration of /"diabetes"/. A statistically significant increase was found in the allele frequency of the interleukin 1B*2 allele in cases compared to controls (chi2=7. 19, df.=1; P=0.007, Pcorr=0.028). The results of this study suggest that the interleukin 1B*2 allele, or a susceptibility factor in linkage disequilibrium with this allele, is associated with diabetic nephropathy in the Northern Ireland population.
|
[
{
"begin_idx": "515",
"end_idx": "523",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "596",
"end_idx": "604",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "887",
"end_idx": "895",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
},
{
"begin_idx": "94",
"end_idx": "114",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "367",
"end_idx": "387",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "1230",
"end_idx": "1250",
"entity_id": "D003928",
"entity_type": "Disease",
"text_name": "diabetic nephropathy"
},
{
"begin_idx": "528",
"end_idx": "539",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "nephropathy"
},
{
"begin_idx": "613",
"end_idx": "624",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "nephropathy"
},
{
"begin_idx": "129",
"end_idx": "142",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1"
},
{
"begin_idx": "292",
"end_idx": "305",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1"
},
{
"begin_idx": "721",
"end_idx": "811",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"
},
{
"begin_idx": "721",
"end_idx": "811",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1A, interleukin 1B, interleukin 1 (type 1) receptor and interleukin 1 receptor"
},
{
"begin_idx": "975",
"end_idx": "989",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1B"
},
{
"begin_idx": "1115",
"end_idx": "1129",
"entity_id": "3553",
"entity_type": "Gene",
"text_name": "interleukin 1B"
}
] |
{
"begin_idx": "292",
"end_idx": "305",
"entity_id": "3552",
"entity_type": "Gene",
"text_name": "interleukin 1"
}
|
{
"begin_idx": "515",
"end_idx": "523",
"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
}
|
No
|
10050867
|
Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer.
|
BACKGROUND: Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers. METHODS: Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50). BRCA1 gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided. RESULTS AND CONCLUSIONS: Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline BRCA1 mutations demonstrated nonrandom X-chromosome inactivation (.0002 < P < .008, for simultaneous occurrence of both). IMPLICATIONS: Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, ovarian cancer.
|
Association between nonrandom X-chromosome inactivation and /"BRCA1"/ mutation in germline DNA of patients with /"ovarian cancer"/.
|
BACKGROUND: Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of /"hereditary ovarian cancers"/. METHODS: Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) /"ovarian cancer"/ and control subjects without a personal or family history of cancer (n = 50). /"BRCA1"/ gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided. RESULTS AND CONCLUSIONS: Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline /"BRCA1"/ mutations demonstrated nonrandom X-chromosome inactivation (.0002 < P < .008, for simultaneous occurrence of both). IMPLICATIONS: Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, /"ovarian cancer"/.
|
[
{
"begin_idx": "1718",
"end_idx": "1733",
"entity_id": "D009362",
"entity_type": "Disease",
"text_name": "invasive cancer"
},
{
"begin_idx": "497",
"end_idx": "502",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
},
{
"begin_idx": "1396",
"end_idx": "1402",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "cancer"
},
{
"begin_idx": "1770",
"end_idx": "1776",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "cancer"
},
{
"begin_idx": "859",
"end_idx": "877",
"entity_id": "D009386",
"entity_type": "Disease",
"text_name": "hereditary cancers"
},
{
"begin_idx": "108",
"end_idx": "122",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "959",
"end_idx": "985",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "hereditary ovarian cancers"
},
{
"begin_idx": "1320",
"end_idx": "1334",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "2199",
"end_idx": "2213",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "1138",
"end_idx": "1155",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "androgen receptor"
},
{
"begin_idx": "1157",
"end_idx": "1159",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "1630",
"end_idx": "1632",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "1909",
"end_idx": "1911",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "60",
"end_idx": "65",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
},
{
"begin_idx": "1413",
"end_idx": "1418",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
},
{
"begin_idx": "1945",
"end_idx": "1950",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
}
] |
{
"begin_idx": "60",
"end_idx": "65",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
}
|
{
"begin_idx": "959",
"end_idx": "985",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "hereditary ovarian cancers"
}
|
Yes
|
10050867
|
Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer.
|
BACKGROUND: Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers. METHODS: Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50). BRCA1 gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided. RESULTS AND CONCLUSIONS: Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline BRCA1 mutations demonstrated nonrandom X-chromosome inactivation (.0002 < P < .008, for simultaneous occurrence of both). IMPLICATIONS: Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, ovarian cancer.
|
Association between nonrandom X-chromosome inactivation and /"BRCA1"/ mutation in germline DNA of patients with ovarian cancer.
|
BACKGROUND: Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of /"hereditary cancers"/. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers. METHODS: Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50). /"BRCA1"/ gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided. RESULTS AND CONCLUSIONS: Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline /"BRCA1"/ mutations demonstrated nonrandom X-chromosome inactivation (.0002 < P < .008, for simultaneous occurrence of both). IMPLICATIONS: Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, ovarian cancer.
|
[
{
"begin_idx": "1718",
"end_idx": "1733",
"entity_id": "D009362",
"entity_type": "Disease",
"text_name": "invasive cancer"
},
{
"begin_idx": "497",
"end_idx": "502",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
},
{
"begin_idx": "1396",
"end_idx": "1402",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "cancer"
},
{
"begin_idx": "1770",
"end_idx": "1776",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "cancer"
},
{
"begin_idx": "859",
"end_idx": "877",
"entity_id": "D009386",
"entity_type": "Disease",
"text_name": "hereditary cancers"
},
{
"begin_idx": "108",
"end_idx": "122",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "959",
"end_idx": "985",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "hereditary ovarian cancers"
},
{
"begin_idx": "1320",
"end_idx": "1334",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "2199",
"end_idx": "2213",
"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "ovarian cancer"
},
{
"begin_idx": "1138",
"end_idx": "1155",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "androgen receptor"
},
{
"begin_idx": "1157",
"end_idx": "1159",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "1630",
"end_idx": "1632",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "1909",
"end_idx": "1911",
"entity_id": "367",
"entity_type": "Gene",
"text_name": "AR"
},
{
"begin_idx": "60",
"end_idx": "65",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
},
{
"begin_idx": "1413",
"end_idx": "1418",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
},
{
"begin_idx": "1945",
"end_idx": "1950",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
}
] |
{
"begin_idx": "1413",
"end_idx": "1418",
"entity_id": "672",
"entity_type": "Gene",
"text_name": "BRCA1"
}
|
{
"begin_idx": "859",
"end_idx": "877",
"entity_id": "D009386",
"entity_type": "Disease",
"text_name": "hereditary cancers"
}
|
No
|
10051017
|
A mutation in the RIEG1 gene associated with Peters' anomaly.
|
Mutations within the RIEG1 homeobox gene on chromosome 4q25 have previously been reported in association with Rieger syndrome. We report a 3' splice site mutation within the 3rd intron of the RIEG1 gene which is associated with unilateral Peters' anomaly. The mutation is a single base substition of A to T at the invariant -2 site of the 3' splice site. Peters' anomaly, which is characterised by ocular anterior segment dysgenesis and central corneal opacification, is distinct from Rieger anomaly. This is the first description of a RIEG1 mutation associated with Peters' anomaly.
|
A mutation in the /"RIEG1"/ gene associated with /"Peters' anomaly"/.
|
Mutations within the /"RIEG1"/ homeobox gene on chromosome 4q25 have previously been reported in association with Rieger syndrome. We report a 3' splice site mutation within the 3rd intron of the /"RIEG1"/ gene which is associated with unilateral /"Peters' anomaly"/. The mutation is a single base substition of A to T at the invariant -2 site of the 3' splice site. /"Peters' anomaly"/, which is characterised by ocular anterior segment dysgenesis and central corneal opacification, is distinct from Rieger anomaly. This is the first description of a /"RIEG1"/ mutation associated with /"Peters' anomaly"/.
|
[
{
"begin_idx": "172",
"end_idx": "187",
"entity_id": "C535679",
"entity_type": "Disease",
"text_name": "Rieger syndrome"
},
{
"begin_idx": "547",
"end_idx": "561",
"entity_id": "C535679",
"entity_type": "Disease",
"text_name": "Rieger anomaly"
},
{
"begin_idx": "45",
"end_idx": "60",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "301",
"end_idx": "316",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "417",
"end_idx": "432",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "629",
"end_idx": "644",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "484",
"end_idx": "494",
"entity_id": "D050033",
"entity_type": "Disease",
"text_name": "dysgenesis"
},
{
"begin_idx": "18",
"end_idx": "23",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "83",
"end_idx": "88",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "254",
"end_idx": "259",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "598",
"end_idx": "603",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
}
] |
{
"begin_idx": "18",
"end_idx": "23",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
}
|
{
"begin_idx": "45",
"end_idx": "60",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
}
|
Yes
|
10051017
|
A mutation in the RIEG1 gene associated with Peters' anomaly.
|
Mutations within the RIEG1 homeobox gene on chromosome 4q25 have previously been reported in association with Rieger syndrome. We report a 3' splice site mutation within the 3rd intron of the RIEG1 gene which is associated with unilateral Peters' anomaly. The mutation is a single base substition of A to T at the invariant -2 site of the 3' splice site. Peters' anomaly, which is characterised by ocular anterior segment dysgenesis and central corneal opacification, is distinct from Rieger anomaly. This is the first description of a RIEG1 mutation associated with Peters' anomaly.
|
A mutation in the /"RIEG1"/ gene associated with Peters' anomaly.
|
Mutations within the /"RIEG1"/ homeobox gene on chromosome 4q25 have previously been reported in association with /"Rieger syndrome"/. We report a 3' splice site mutation within the 3rd intron of the /"RIEG1"/ gene which is associated with unilateral Peters' anomaly. The mutation is a single base substition of A to T at the invariant -2 site of the 3' splice site. Peters' anomaly, which is characterised by ocular anterior segment dysgenesis and central corneal opacification, is distinct from /"Rieger anomaly"/. This is the first description of a /"RIEG1"/ mutation associated with Peters' anomaly.
|
[
{
"begin_idx": "172",
"end_idx": "187",
"entity_id": "C535679",
"entity_type": "Disease",
"text_name": "Rieger syndrome"
},
{
"begin_idx": "547",
"end_idx": "561",
"entity_id": "C535679",
"entity_type": "Disease",
"text_name": "Rieger anomaly"
},
{
"begin_idx": "45",
"end_idx": "60",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "301",
"end_idx": "316",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "417",
"end_idx": "432",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "629",
"end_idx": "644",
"entity_id": "C537884",
"entity_type": "Disease",
"text_name": "Peters' anomaly"
},
{
"begin_idx": "484",
"end_idx": "494",
"entity_id": "D050033",
"entity_type": "Disease",
"text_name": "dysgenesis"
},
{
"begin_idx": "18",
"end_idx": "23",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "83",
"end_idx": "88",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "254",
"end_idx": "259",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
},
{
"begin_idx": "598",
"end_idx": "603",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
}
] |
{
"begin_idx": "83",
"end_idx": "88",
"entity_id": "5308",
"entity_type": "Gene",
"text_name": "RIEG1"
}
|
{
"begin_idx": "547",
"end_idx": "561",
"entity_id": "C535679",
"entity_type": "Disease",
"text_name": "Rieger anomaly"
}
|
No
|
10051160
|
Severe Lhermitte-Duclos disease with unique germline mutation of PTEN.
|
Germline mutations in the PTEN gene have recently been identified in some individuals with Cowden disease (CD), Lhermitte-Duclos disease (LDD), and Bannayan-Zonana syndrome. We report on a patient with CD and LDD in whom a unique de novo germline missense mutation is present in the PTEN gene. Direct sequence analysis detected a transitional change (T-->C) at nucleotide 335, resulting in substitution of the amino acid proline for leucine. The mutation is in exon 5, which has been proposed as a "hot-spot" for germline mutations. Comparison of this patient's clinical course with the previously reported cases of CD and LDD shows more extensive and more severe clinical findings than reported previously. Findings in this patient contribute to the current understanding of germline PTEN mutations and clinical outcome.
|
Severe /"Lhermitte-Duclos disease"/ with unique germline mutation of /"PTEN"/.
|
Germline mutations in the /"PTEN"/ gene have recently been identified in some individuals with /"Cowden disease"/ (/"CD"/), /"Lhermitte-Duclos disease"/ (/"LDD"/), and /"Bannayan-Zonana syndrome"/. We report on a patient with /"CD"/ and /"LDD"/ in whom a unique de novo germline missense mutation is present in the /"PTEN"/ gene. Direct sequence analysis detected a transitional change (T-->C) at nucleotide 335, resulting in substitution of the amino acid proline for leucine. The mutation is in exon 5, which has been proposed as a "hot-spot" for germline mutations. Comparison of this patient's clinical course with the previously reported cases of /"CD"/ and /"LDD"/ shows more extensive and more severe clinical findings than reported previously. Findings in this patient contribute to the current understanding of germline /"PTEN"/ mutations and clinical outcome.
|
[
{
"begin_idx": "7",
"end_idx": "31",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "Lhermitte-Duclos disease"
},
{
"begin_idx": "162",
"end_idx": "176",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "Cowden disease"
},
{
"begin_idx": "178",
"end_idx": "180",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "CD"
},
{
"begin_idx": "183",
"end_idx": "207",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "Lhermitte-Duclos disease"
},
{
"begin_idx": "209",
"end_idx": "212",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "LDD"
},
{
"begin_idx": "219",
"end_idx": "243",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "Bannayan-Zonana syndrome"
},
{
"begin_idx": "273",
"end_idx": "275",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "CD"
},
{
"begin_idx": "280",
"end_idx": "283",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "LDD"
},
{
"begin_idx": "687",
"end_idx": "689",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "CD"
},
{
"begin_idx": "694",
"end_idx": "697",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "LDD"
},
{
"begin_idx": "65",
"end_idx": "69",
"entity_id": "5728",
"entity_type": "Gene",
"text_name": "PTEN"
},
{
"begin_idx": "97",
"end_idx": "101",
"entity_id": "5728",
"entity_type": "Gene",
"text_name": "PTEN"
},
{
"begin_idx": "354",
"end_idx": "358",
"entity_id": "5728",
"entity_type": "Gene",
"text_name": "PTEN"
},
{
"begin_idx": "856",
"end_idx": "860",
"entity_id": "5728",
"entity_type": "Gene",
"text_name": "PTEN"
}
] |
{
"begin_idx": "65",
"end_idx": "69",
"entity_id": "5728",
"entity_type": "Gene",
"text_name": "PTEN"
}
|
{
"begin_idx": "7",
"end_idx": "31",
"entity_id": "D006223",
"entity_type": "Disease",
"text_name": "Lhermitte-Duclos disease"
}
|
Yes
|
10051604
|
Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.
|
At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that PEX19 is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.
|
Human /"PEX19"/: cDNA cloning by functional complementation, mutation analysis in a patient with /"Zellweger syndrome"/, and potential role in peroxisomal membrane assembly.
|
At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as /"Zellweger syndrome"/, for which seven pathogenic genes have been elucidated. We have isolated a human /"PEX19"/ cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (/"Pex19p"/) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated /"Pex19p"/ is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with /"Zellweger syndrome"/ of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal /"Pex19p"/. These results demonstrate that /"PEX19"/ is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of /"Pex19p"/. Moreover, /"Pex19p"/ is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.
|
[
{
"begin_idx": "93",
"end_idx": "111",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "283",
"end_idx": "301",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "1050",
"end_idx": "1068",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "236",
"end_idx": "267",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "peroxisome biogenesis disorders"
},
{
"begin_idx": "269",
"end_idx": "273",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "PBDs"
},
{
"begin_idx": "437",
"end_idx": "458",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "peroxisome deficiency"
},
{
"begin_idx": "6",
"end_idx": "11",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "383",
"end_idx": "388",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "610",
"end_idx": "616",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "714",
"end_idx": "720",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1279",
"end_idx": "1285",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1318",
"end_idx": "1323",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "1473",
"end_idx": "1479",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1491",
"end_idx": "1497",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
}
] |
{
"begin_idx": "610",
"end_idx": "616",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
}
|
{
"begin_idx": "93",
"end_idx": "111",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
}
|
Yes
|
10051604
|
Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.
|
At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that PEX19 is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.
|
Human /"PEX19"/: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.
|
At least 11 complementation groups (CGs) have been identified for the /"peroxisome biogenesis disorders"/ (/"PBDs"/) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human /"PEX19"/ cDNA (HsPEX19) by functional complementation of /"peroxisome deficiency"/ of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (/"Pex19p"/) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated /"Pex19p"/ is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal /"Pex19p"/. These results demonstrate that /"PEX19"/ is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of /"Pex19p"/. Moreover, /"Pex19p"/ is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.
|
[
{
"begin_idx": "93",
"end_idx": "111",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "283",
"end_idx": "301",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "1050",
"end_idx": "1068",
"entity_id": "D015211",
"entity_type": "Disease",
"text_name": "Zellweger syndrome"
},
{
"begin_idx": "236",
"end_idx": "267",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "peroxisome biogenesis disorders"
},
{
"begin_idx": "269",
"end_idx": "273",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "PBDs"
},
{
"begin_idx": "437",
"end_idx": "458",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "peroxisome deficiency"
},
{
"begin_idx": "6",
"end_idx": "11",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "383",
"end_idx": "388",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "610",
"end_idx": "616",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "714",
"end_idx": "720",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1279",
"end_idx": "1285",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1318",
"end_idx": "1323",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "PEX19"
},
{
"begin_idx": "1473",
"end_idx": "1479",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
},
{
"begin_idx": "1491",
"end_idx": "1497",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
}
] |
{
"begin_idx": "1491",
"end_idx": "1497",
"entity_id": "5824",
"entity_type": "Gene",
"text_name": "Pex19p"
}
|
{
"begin_idx": "236",
"end_idx": "267",
"entity_id": "D018901",
"entity_type": "Disease",
"text_name": "peroxisome biogenesis disorders"
}
|
No
|
10053004
|
Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.
|
Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished types of MoCo deficiency that have an identical phenotype. Both types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in MoCo-deficient patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified MOCS2 mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified MOCS2 mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.
|
Human molybdopterin synthase gene: genomic structure and mutations in molybdenum /"cofactor deficiency type B"/.
|
Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished types of MoCo deficiency that have an identical phenotype. Both types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). /"MOCS2"/ encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in MoCo-deficient patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified /"MOCS2"/ mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified /"MOCS2"/ mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.
|
[
{
"begin_idx": "416",
"end_idx": "440",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "types of MoCo deficiency"
},
{
"begin_idx": "480",
"end_idx": "504",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "types of MoCo deficiency"
},
{
"begin_idx": "1073",
"end_idx": "1087",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "MoCo-deficient"
},
{
"begin_idx": "1788",
"end_idx": "1803",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "MoCo deficiency"
},
{
"begin_idx": "81",
"end_idx": "107",
"entity_id": "C565373",
"entity_type": "Disease",
"text_name": "cofactor deficiency type B"
},
{
"begin_idx": "583",
"end_idx": "602",
"entity_id": "D009422",
"entity_type": "Disease",
"text_name": "neurological damage"
},
{
"begin_idx": "604",
"end_idx": "609",
"entity_id": "4337",
"entity_type": "Gene",
"text_name": "MOCS1"
},
{
"begin_idx": "1127",
"end_idx": "1132",
"entity_id": "4337",
"entity_type": "Gene",
"text_name": "MOCS1"
},
{
"begin_idx": "798",
"end_idx": "803",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
},
{
"begin_idx": "1229",
"end_idx": "1234",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
},
{
"begin_idx": "1644",
"end_idx": "1649",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
}
] |
{
"begin_idx": "798",
"end_idx": "803",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
}
|
{
"begin_idx": "81",
"end_idx": "107",
"entity_id": "C565373",
"entity_type": "Disease",
"text_name": "cofactor deficiency type B"
}
|
Yes
|
10053004
|
Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.
|
Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished types of MoCo deficiency that have an identical phenotype. Both types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in MoCo-deficient patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified MOCS2 mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified MOCS2 mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.
|
Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.
|
Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished /"types of MoCo deficiency"/ that have an identical phenotype. Both /"types of MoCo deficiency"/ result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). /"MOCS2"/ encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in /"MoCo-deficient"/ patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified /"MOCS2"/ mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified /"MOCS2"/ mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of /"MoCo deficiency"/, that formerly had been established by cell-culture experiments.
|
[
{
"begin_idx": "416",
"end_idx": "440",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "types of MoCo deficiency"
},
{
"begin_idx": "480",
"end_idx": "504",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "types of MoCo deficiency"
},
{
"begin_idx": "1073",
"end_idx": "1087",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "MoCo-deficient"
},
{
"begin_idx": "1788",
"end_idx": "1803",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "MoCo deficiency"
},
{
"begin_idx": "81",
"end_idx": "107",
"entity_id": "C565373",
"entity_type": "Disease",
"text_name": "cofactor deficiency type B"
},
{
"begin_idx": "583",
"end_idx": "602",
"entity_id": "D009422",
"entity_type": "Disease",
"text_name": "neurological damage"
},
{
"begin_idx": "604",
"end_idx": "609",
"entity_id": "4337",
"entity_type": "Gene",
"text_name": "MOCS1"
},
{
"begin_idx": "1127",
"end_idx": "1132",
"entity_id": "4337",
"entity_type": "Gene",
"text_name": "MOCS1"
},
{
"begin_idx": "798",
"end_idx": "803",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
},
{
"begin_idx": "1229",
"end_idx": "1234",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
},
{
"begin_idx": "1644",
"end_idx": "1649",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
}
] |
{
"begin_idx": "798",
"end_idx": "803",
"entity_id": "4338",
"entity_type": "Gene",
"text_name": "MOCS2"
}
|
{
"begin_idx": "1073",
"end_idx": "1087",
"entity_id": "C535811",
"entity_type": "Disease",
"text_name": "MoCo-deficient"
}
|
No
|
10053008
|
Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.
|
Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.
|
Genomic structure of the canalicular multispecific organic anion-transporter gene (/"MRP2"///"cMOAT"/) and mutations in the ATP-binding-cassette region in /"Dubin-Johnson syndrome"/.
|
/"Dubin-Johnson syndrome"/ (/"DJS"/) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (/"MRP2"///"cMOAT"/) in patients with /"DJS"/ have suggested that the gene defects are responsible for /"DJS"/. In this study, we determined the exon/intron structure of the human /"MRP2"///"cMOAT"/ gene and further characterized mutations in patients with /"DJS"/. The human /"MRP2"///"cMOAT"/ gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that /"MRP2"///"cMOAT"/ is the gene responsible for /"DJS"/. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.
|
[
{
"begin_idx": "262",
"end_idx": "280",
"entity_id": "D006932",
"entity_type": "Disease",
"text_name": "hyperbilirubinemia"
},
{
"begin_idx": "147",
"end_idx": "169",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "Dubin-Johnson syndrome"
},
{
"begin_idx": "171",
"end_idx": "193",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "Dubin-Johnson syndrome"
},
{
"begin_idx": "195",
"end_idx": "198",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "414",
"end_idx": "417",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "475",
"end_idx": "478",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "617",
"end_idx": "620",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "1116",
"end_idx": "1119",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "206",
"end_idx": "233",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disease"
},
{
"begin_idx": "83",
"end_idx": "87",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "88",
"end_idx": "93",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "385",
"end_idx": "389",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "390",
"end_idx": "395",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "548",
"end_idx": "552",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "553",
"end_idx": "558",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "632",
"end_idx": "636",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "637",
"end_idx": "642",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "1077",
"end_idx": "1081",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "1082",
"end_idx": "1087",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "774",
"end_idx": "813",
"entity_id": "8714",
"entity_type": "Gene",
"text_name": "multidrug resistance-associated protein"
}
] |
{
"begin_idx": "88",
"end_idx": "93",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
}
|
{
"begin_idx": "147",
"end_idx": "169",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "Dubin-Johnson syndrome"
}
|
Yes
|
10053008
|
Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.
|
Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.
|
Genomic structure of the canalicular multispecific organic anion-transporter gene (/"MRP2"///"cMOAT"/) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.
|
Dubin-Johnson syndrome (DJS) is an /"autosomal recessive disease"/ characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (/"MRP2"///"cMOAT"/) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human /"MRP2"///"cMOAT"/ gene and further characterized mutations in patients with DJS. The human /"MRP2"///"cMOAT"/ gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that /"MRP2"///"cMOAT"/ is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.
|
[
{
"begin_idx": "262",
"end_idx": "280",
"entity_id": "D006932",
"entity_type": "Disease",
"text_name": "hyperbilirubinemia"
},
{
"begin_idx": "147",
"end_idx": "169",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "Dubin-Johnson syndrome"
},
{
"begin_idx": "171",
"end_idx": "193",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "Dubin-Johnson syndrome"
},
{
"begin_idx": "195",
"end_idx": "198",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "414",
"end_idx": "417",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "475",
"end_idx": "478",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "617",
"end_idx": "620",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "1116",
"end_idx": "1119",
"entity_id": "D007566",
"entity_type": "Disease",
"text_name": "DJS"
},
{
"begin_idx": "206",
"end_idx": "233",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disease"
},
{
"begin_idx": "83",
"end_idx": "87",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "88",
"end_idx": "93",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "385",
"end_idx": "389",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "390",
"end_idx": "395",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "548",
"end_idx": "552",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "553",
"end_idx": "558",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "632",
"end_idx": "636",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "637",
"end_idx": "642",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "1077",
"end_idx": "1081",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "MRP2"
},
{
"begin_idx": "1082",
"end_idx": "1087",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
},
{
"begin_idx": "774",
"end_idx": "813",
"entity_id": "8714",
"entity_type": "Gene",
"text_name": "multidrug resistance-associated protein"
}
] |
{
"begin_idx": "553",
"end_idx": "558",
"entity_id": "1244",
"entity_type": "Gene",
"text_name": "cMOAT"
}
|
{
"begin_idx": "206",
"end_idx": "233",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal recessive disease"
}
|
No
|
10069705
|
Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack of loss of heterozygosity in a lung cyst.
|
A Japanese patient with tuberous sclerosis (TSC), who manifested with multiple lung cysts and pneumothorax, is described. All exons of two TSC genes, TSC1 and TSC2, in peripheral blood leukocytes from the patient were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). A novel T-to-G transition was found in exon 19 of TSC2 at nucleotide position 2168. This mutation caused an amino acid change, L717R. There was no such mutation in any other family members or in 100 normal Japanese. An automated sequencer-assisted quantitative analysis of normal and mutated SSCP-bands revealed no loss of heterozygosity (LOH) in the lung cyst tissue of the patient.
|
Novel /"TSC2"/C2"/ mutation in a patient with pulmonary tuberous sclerosis: lack of loss of heterozygosity in a lung cyst.
|
A Japanese patient with tuberous sclerosis (TSC), who manifested with multiple lung cysts and pneumothorax, is described. All exons of two TSC genes, TSC1 and /"TSC2"/C2"/, in peripheral blood leukocytes from the patient were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). A novel T-to-G transition was found in exon 19 of /"TSC2"/C2"/ at nucleotide position 2168. This mutation caused an amino acid change, L717R. There was no such mutation in any other family members or in 100 normal Japanese. An automated sequencer-assisted quantitative analysis of normal and mutated SSCP-bands revealed no loss of heterozygosity (LOH) in the lung cyst tissue of the patient.
|
[
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "274",
"end_idx": "278",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "473",
"end_idx": "477",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "104",
"end_idx": "113",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "lung cyst"
},
{
"begin_idx": "185",
"end_idx": "204",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "multiple lung cysts"
},
{
"begin_idx": "774",
"end_idx": "783",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "lung cyst"
},
{
"begin_idx": "38",
"end_idx": "66",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "pulmonary tuberous sclerosis"
},
{
"begin_idx": "139",
"end_idx": "157",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "tuberous sclerosis"
},
{
"begin_idx": "159",
"end_idx": "162",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "TSC"
},
{
"begin_idx": "254",
"end_idx": "257",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "TSC"
},
{
"begin_idx": "265",
"end_idx": "269",
"entity_id": "7248",
"entity_type": "Gene",
"text_name": "TSC1"
},
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
},
{
"begin_idx": "274",
"end_idx": "278",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
},
{
"begin_idx": "473",
"end_idx": "477",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
}
] |
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
}
|
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
}
|
Yes
|
10069705
|
Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack of loss of heterozygosity in a lung cyst.
|
A Japanese patient with tuberous sclerosis (TSC), who manifested with multiple lung cysts and pneumothorax, is described. All exons of two TSC genes, TSC1 and TSC2, in peripheral blood leukocytes from the patient were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). A novel T-to-G transition was found in exon 19 of TSC2 at nucleotide position 2168. This mutation caused an amino acid change, L717R. There was no such mutation in any other family members or in 100 normal Japanese. An automated sequencer-assisted quantitative analysis of normal and mutated SSCP-bands revealed no loss of heterozygosity (LOH) in the lung cyst tissue of the patient.
|
Novel /"TSC2"/ mutation in a patient with /"pulmonary tuberous sclerosis"/: lack of loss of heterozygosity in a lung cyst.
|
A Japanese patient with /"tuberous sclerosis"/ (/"TSC"/), who manifested with multiple lung cysts and pneumothorax, is described. All exons of two /"TSC"/ genes, TSC1 and /"TSC2"/, in peripheral blood leukocytes from the patient were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). A novel T-to-G transition was found in exon 19 of /"TSC2"/ at nucleotide position 2168. This mutation caused an amino acid change, L717R. There was no such mutation in any other family members or in 100 normal Japanese. An automated sequencer-assisted quantitative analysis of normal and mutated SSCP-bands revealed no loss of heterozygosity (LOH) in the lung cyst tissue of the patient.
|
[
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "274",
"end_idx": "278",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "473",
"end_idx": "477",
"entity_id": "C566021",
"entity_type": "Disease",
"text_name": "TSC2"
},
{
"begin_idx": "104",
"end_idx": "113",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "lung cyst"
},
{
"begin_idx": "185",
"end_idx": "204",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "multiple lung cysts"
},
{
"begin_idx": "774",
"end_idx": "783",
"entity_id": "D008171",
"entity_type": "Disease",
"text_name": "lung cyst"
},
{
"begin_idx": "38",
"end_idx": "66",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "pulmonary tuberous sclerosis"
},
{
"begin_idx": "139",
"end_idx": "157",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "tuberous sclerosis"
},
{
"begin_idx": "159",
"end_idx": "162",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "TSC"
},
{
"begin_idx": "254",
"end_idx": "257",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "TSC"
},
{
"begin_idx": "265",
"end_idx": "269",
"entity_id": "7248",
"entity_type": "Gene",
"text_name": "TSC1"
},
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
},
{
"begin_idx": "274",
"end_idx": "278",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
},
{
"begin_idx": "473",
"end_idx": "477",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
}
] |
{
"begin_idx": "6",
"end_idx": "10",
"entity_id": "7249",
"entity_type": "Gene",
"text_name": "TSC2"
}
|
{
"begin_idx": "38",
"end_idx": "66",
"entity_id": "D014402",
"entity_type": "Disease",
"text_name": "pulmonary tuberous sclerosis"
}
|
No
|
10071100
|
Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene.
|
BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited motor and sensory neuropathy that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein connexin 32 (Cx32). Cx32 is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a Cx32 mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of Cx32. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and Cx32 mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of CMTX and a search for gene mutations towards Cx32 should be considered.
|
Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the /"connexin 32"/ gene.
|
BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited motor and sensory neuropathy that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein /"connexin 32"/ (/"Cx32"/). /"Cx32"/ is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a /"Cx32"/ mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of /"Cx32"/. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and /"Cx32"/ mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of /"CMTX"/ and a search for gene mutations towards /"Cx32"/ should be considered.
|
[
{
"begin_idx": "1350",
"end_idx": "1354",
"entity_id": "C535919",
"entity_type": "Disease",
"text_name": "CMTX"
},
{
"begin_idx": "61",
"end_idx": "80",
"entity_id": "D002607",
"entity_type": "Disease",
"text_name": "Charcot-Marie-Tooth"
},
{
"begin_idx": "170",
"end_idx": "197",
"entity_id": "D002607",
"entity_type": "Disease",
"text_name": "Charcot-Marie-Tooth disease"
},
{
"begin_idx": "212",
"end_idx": "250",
"entity_id": "D010523",
"entity_type": "Disease",
"text_name": "inherited motor and sensory neuropathy"
},
{
"begin_idx": "122",
"end_idx": "133",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "connexin 32"
},
{
"begin_idx": "365",
"end_idx": "376",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "connexin 32"
},
{
"begin_idx": "378",
"end_idx": "382",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "385",
"end_idx": "389",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "527",
"end_idx": "531",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "762",
"end_idx": "766",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "1237",
"end_idx": "1241",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "1395",
"end_idx": "1399",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "302",
"end_idx": "306",
"entity_id": "4359",
"entity_type": "Gene",
"text_name": "CMT1"
},
{
"begin_idx": "507",
"end_idx": "511",
"entity_id": "4359",
"entity_type": "Gene",
"text_name": "CMT1"
}
] |
{
"begin_idx": "122",
"end_idx": "133",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "connexin 32"
}
|
{
"begin_idx": "1350",
"end_idx": "1354",
"entity_id": "C535919",
"entity_type": "Disease",
"text_name": "CMTX"
}
|
Yes
|
10071100
|
Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene.
|
BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited motor and sensory neuropathy that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein connexin 32 (Cx32). Cx32 is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a Cx32 mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of Cx32. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and Cx32 mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of CMTX and a search for gene mutations towards Cx32 should be considered.
|
Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the /"connexin 32"/ gene.
|
BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an /"inherited motor and sensory neuropathy"/ that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein /"connexin 32"/ (/"Cx32"/). /"Cx32"/ is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a /"Cx32"/ mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of /"Cx32"/. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and /"Cx32"/ mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of CMTX and a search for gene mutations towards /"Cx32"/ should be considered.
|
[
{
"begin_idx": "1350",
"end_idx": "1354",
"entity_id": "C535919",
"entity_type": "Disease",
"text_name": "CMTX"
},
{
"begin_idx": "61",
"end_idx": "80",
"entity_id": "D002607",
"entity_type": "Disease",
"text_name": "Charcot-Marie-Tooth"
},
{
"begin_idx": "170",
"end_idx": "197",
"entity_id": "D002607",
"entity_type": "Disease",
"text_name": "Charcot-Marie-Tooth disease"
},
{
"begin_idx": "212",
"end_idx": "250",
"entity_id": "D010523",
"entity_type": "Disease",
"text_name": "inherited motor and sensory neuropathy"
},
{
"begin_idx": "122",
"end_idx": "133",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "connexin 32"
},
{
"begin_idx": "365",
"end_idx": "376",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "connexin 32"
},
{
"begin_idx": "378",
"end_idx": "382",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "385",
"end_idx": "389",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "527",
"end_idx": "531",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "762",
"end_idx": "766",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "1237",
"end_idx": "1241",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "1395",
"end_idx": "1399",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
},
{
"begin_idx": "302",
"end_idx": "306",
"entity_id": "4359",
"entity_type": "Gene",
"text_name": "CMT1"
},
{
"begin_idx": "507",
"end_idx": "511",
"entity_id": "4359",
"entity_type": "Gene",
"text_name": "CMT1"
}
] |
{
"begin_idx": "762",
"end_idx": "766",
"entity_id": "2705",
"entity_type": "Gene",
"text_name": "Cx32"
}
|
{
"begin_idx": "212",
"end_idx": "250",
"entity_id": "D010523",
"entity_type": "Disease",
"text_name": "inherited motor and sensory neuropathy"
}
|
No
|
10072423
|
A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
|
Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.
|
A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
|
/"Autosomal recessive juvenile parkinsonism"/ (/"AR-JP"/JP"/, /"PARK2"/; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for /"AR-JP"/JP"/ was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.
|
[
{
"begin_idx": "509",
"end_idx": "520",
"entity_id": "D004409",
"entity_type": "Disease",
"text_name": "dyskinesias"
},
{
"begin_idx": "67",
"end_idx": "99",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "118",
"end_idx": "137",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's Disease"
},
{
"begin_idx": "216",
"end_idx": "235",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's Disease"
},
{
"begin_idx": "338",
"end_idx": "357",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "359",
"end_idx": "361",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "704",
"end_idx": "736",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "1827",
"end_idx": "1829",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1936",
"end_idx": "1968",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "1736",
"end_idx": "1748",
"entity_id": "D010302",
"entity_type": "Disease",
"text_name": "parkinsonism"
},
{
"begin_idx": "237",
"end_idx": "278",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "Autosomal recessive juvenile parkinsonism"
},
{
"begin_idx": "280",
"end_idx": "285",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "AR-JP"
},
{
"begin_idx": "547",
"end_idx": "552",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "AR-JP"
},
{
"begin_idx": "280",
"end_idx": "285",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
},
{
"begin_idx": "287",
"end_idx": "292",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "PARK2"
},
{
"begin_idx": "547",
"end_idx": "552",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
}
] |
{
"begin_idx": "280",
"end_idx": "285",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
}
|
{
"begin_idx": "237",
"end_idx": "278",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "Autosomal recessive juvenile parkinsonism"
}
|
Yes
|
10072423
|
A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
|
Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.
|
A wide variety of mutations in the parkin gene are responsible for /"autosomal recessive parkinsonism"/ in Europe. French /"Parkinson's Disease"/ Genetics Study Group and the European Consortium on Genetic Susceptibility in /"Parkinson's Disease"/.
|
Autosomal recessive juvenile parkinsonism (/"AR-JP"/, /"PARK2"/; OMIM 602544), one of the monogenic forms of /"Parkinson's disease"/ (/"PD"/), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for /"AR-JP"/ was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset /"autosomal recessive parkinsonism"/. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic /"PD"/. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of /"autosomal recessive parkinsonism"/ in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.
|
[
{
"begin_idx": "509",
"end_idx": "520",
"entity_id": "D004409",
"entity_type": "Disease",
"text_name": "dyskinesias"
},
{
"begin_idx": "67",
"end_idx": "99",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "118",
"end_idx": "137",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's Disease"
},
{
"begin_idx": "216",
"end_idx": "235",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's Disease"
},
{
"begin_idx": "338",
"end_idx": "357",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "359",
"end_idx": "361",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "704",
"end_idx": "736",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "1827",
"end_idx": "1829",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1936",
"end_idx": "1968",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "autosomal recessive parkinsonism"
},
{
"begin_idx": "1736",
"end_idx": "1748",
"entity_id": "D010302",
"entity_type": "Disease",
"text_name": "parkinsonism"
},
{
"begin_idx": "237",
"end_idx": "278",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "Autosomal recessive juvenile parkinsonism"
},
{
"begin_idx": "280",
"end_idx": "285",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "AR-JP"
},
{
"begin_idx": "547",
"end_idx": "552",
"entity_id": "D020734",
"entity_type": "Disease",
"text_name": "AR-JP"
},
{
"begin_idx": "280",
"end_idx": "285",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
},
{
"begin_idx": "287",
"end_idx": "292",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "PARK2"
},
{
"begin_idx": "547",
"end_idx": "552",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
}
] |
{
"begin_idx": "547",
"end_idx": "552",
"entity_id": "5071",
"entity_type": "Gene",
"text_name": "AR-JP"
}
|
{
"begin_idx": "1827",
"end_idx": "1829",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
}
|
No
|
10072428
|
Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.
|
Inherited mutations in the E-cadherin gene ( CDH1 ) were described recently in three Maori kindreds with familial gastric cancer. Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non-Maori populations is due to germline CDH1 mutations. Therefore, we screened eight familial gastric cancer kindreds of British and Irish origin for germline CDH1 mutations, by SSCP analysis of all 16 exons and flanking sequences. Each family contained: (i) two cases of gastric cancer in first degree relatives with one affected before age 50 years; or (ii) three or more cases of gastric cancer. Novel germline CDH1 mutations (a nonsense and a splice site) were detected in two families (25%). Both mutations were predicted to truncate the E-cadherin protein in the signal peptide domain. In one family there was evidence of non-penetrance and susceptibility to both gastric and colorectal cancer; thus, in addition to six cases of gastric cancer, a CDH1 mutation carrier developed colorectal cancer at age 30 years. We have confirmed that germline mutations in the CDH1 gene cause familial gastric cancer in non-Maori populations. However, only a minority of familial gastric cancers can be accounted for by CDH1 mutations. Loss of E-cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers, and our findings provide evidence that germline CDH1 mutations predispose to early onset colorectal cancer. Thus, CDH1 should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers.
|
Germline /"E-cadherin"/ gene (/"CDH1"/) mutations predispose to /"familial gastric cancer"/ and colorectal cancer.
|
Inherited mutations in the /"E-cadherin"/ gene ( /"CDH1"/ ) were described recently in three Maori kindreds with /"familial gastric cancer"/. /"Familial gastric cancer"/ is genetically heterogeneous and it is not clear what proportion of /"gastric cancer"/ susceptibility in non-Maori populations is due to germline /"CDH1"/ mutations. Therefore, we screened eight /"familial gastric cancer"/ kindreds of British and Irish origin for germline /"CDH1"/ mutations, by SSCP analysis of all 16 exons and flanking sequences. Each family contained: (i) two cases of /"gastric cancer"/ in first degree relatives with one affected before age 50 years; or (ii) three or more cases of /"gastric cancer"/. Novel germline /"CDH1"/ mutations (a nonsense and a splice site) were detected in two families (25%). Both mutations were predicted to truncate the /"E-cadherin"/ protein in the signal peptide domain. In one family there was evidence of non-penetrance and susceptibility to both gastric and colorectal cancer; thus, in addition to six cases of /"gastric cancer"/, a /"CDH1"/ mutation carrier developed colorectal cancer at age 30 years. We have confirmed that germline mutations in the /"CDH1"/ gene cause /"familial gastric cancer"/ in non-Maori populations. However, only a minority of /"familial gastric cancers"/ can be accounted for by /"CDH1"/ mutations. Loss of /"E-cadherin"/ function has been implicated in the pathogenesis of sporadic colorectal and other cancers, and our findings provide evidence that germline /"CDH1"/ mutations predispose to early onset colorectal cancer. Thus, /"CDH1"/ should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers.
|
[
{
"begin_idx": "56",
"end_idx": "79",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "208",
"end_idx": "231",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "233",
"end_idx": "256",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "Familial gastric cancer"
},
{
"begin_idx": "325",
"end_idx": "339",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "444",
"end_idx": "467",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "631",
"end_idx": "645",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "742",
"end_idx": "756",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "1094",
"end_idx": "1108",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "1244",
"end_idx": "1267",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "1322",
"end_idx": "1346",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancers"
},
{
"begin_idx": "84",
"end_idx": "101",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1029",
"end_idx": "1058",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "gastric and colorectal cancer"
},
{
"begin_idx": "1144",
"end_idx": "1161",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1467",
"end_idx": "1495",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal and other cancers"
},
{
"begin_idx": "1586",
"end_idx": "1603",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1686",
"end_idx": "1716",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "gastric and colorectal cancers"
},
{
"begin_idx": "9",
"end_idx": "19",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "26",
"end_idx": "30",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "130",
"end_idx": "140",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "148",
"end_idx": "152",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "399",
"end_idx": "403",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "518",
"end_idx": "522",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "773",
"end_idx": "777",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "902",
"end_idx": "912",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "1112",
"end_idx": "1116",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1228",
"end_idx": "1232",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1371",
"end_idx": "1375",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1395",
"end_idx": "1405",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "1545",
"end_idx": "1549",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1611",
"end_idx": "1615",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
}
] |
{
"begin_idx": "9",
"end_idx": "19",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
}
|
{
"begin_idx": "1322",
"end_idx": "1346",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancers"
}
|
Yes
|
10072428
|
Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.
|
Inherited mutations in the E-cadherin gene ( CDH1 ) were described recently in three Maori kindreds with familial gastric cancer. Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non-Maori populations is due to germline CDH1 mutations. Therefore, we screened eight familial gastric cancer kindreds of British and Irish origin for germline CDH1 mutations, by SSCP analysis of all 16 exons and flanking sequences. Each family contained: (i) two cases of gastric cancer in first degree relatives with one affected before age 50 years; or (ii) three or more cases of gastric cancer. Novel germline CDH1 mutations (a nonsense and a splice site) were detected in two families (25%). Both mutations were predicted to truncate the E-cadherin protein in the signal peptide domain. In one family there was evidence of non-penetrance and susceptibility to both gastric and colorectal cancer; thus, in addition to six cases of gastric cancer, a CDH1 mutation carrier developed colorectal cancer at age 30 years. We have confirmed that germline mutations in the CDH1 gene cause familial gastric cancer in non-Maori populations. However, only a minority of familial gastric cancers can be accounted for by CDH1 mutations. Loss of E-cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers, and our findings provide evidence that germline CDH1 mutations predispose to early onset colorectal cancer. Thus, CDH1 should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers.
|
Germline /"E-cadherin"/ gene (/"CDH1"/) mutations predispose to familial gastric cancer and /"colorectal cancer"/.
|
Inherited mutations in the /"E-cadherin"/ gene ( /"CDH1"/ ) were described recently in three Maori kindreds with familial gastric cancer. Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non-Maori populations is due to germline /"CDH1"/ mutations. Therefore, we screened eight familial gastric cancer kindreds of British and Irish origin for germline /"CDH1"/ mutations, by SSCP analysis of all 16 exons and flanking sequences. Each family contained: (i) two cases of gastric cancer in first degree relatives with one affected before age 50 years; or (ii) three or more cases of gastric cancer. Novel germline /"CDH1"/ mutations (a nonsense and a splice site) were detected in two families (25%). Both mutations were predicted to truncate the /"E-cadherin"/ protein in the signal peptide domain. In one family there was evidence of non-penetrance and susceptibility to both /"gastric and colorectal cancer"/; thus, in addition to six cases of gastric cancer, a /"CDH1"/ mutation carrier developed /"colorectal cancer"/ at age 30 years. We have confirmed that germline mutations in the /"CDH1"/ gene cause familial gastric cancer in non-Maori populations. However, only a minority of familial gastric cancers can be accounted for by /"CDH1"/ mutations. Loss of /"E-cadherin"/ function has been implicated in the pathogenesis of sporadic /"colorectal and other cancers"/, and our findings provide evidence that germline /"CDH1"/ mutations predispose to early onset /"colorectal cancer"/. Thus, /"CDH1"/ should be investigated as a cause of inherited susceptibility to both /"gastric and colorectal cancers"/.
|
[
{
"begin_idx": "56",
"end_idx": "79",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "208",
"end_idx": "231",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "233",
"end_idx": "256",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "Familial gastric cancer"
},
{
"begin_idx": "325",
"end_idx": "339",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "444",
"end_idx": "467",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "631",
"end_idx": "645",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "742",
"end_idx": "756",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "1094",
"end_idx": "1108",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric cancer"
},
{
"begin_idx": "1244",
"end_idx": "1267",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancer"
},
{
"begin_idx": "1322",
"end_idx": "1346",
"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "familial gastric cancers"
},
{
"begin_idx": "84",
"end_idx": "101",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1029",
"end_idx": "1058",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "gastric and colorectal cancer"
},
{
"begin_idx": "1144",
"end_idx": "1161",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1467",
"end_idx": "1495",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal and other cancers"
},
{
"begin_idx": "1586",
"end_idx": "1603",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
},
{
"begin_idx": "1686",
"end_idx": "1716",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "gastric and colorectal cancers"
},
{
"begin_idx": "9",
"end_idx": "19",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "26",
"end_idx": "30",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "130",
"end_idx": "140",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "148",
"end_idx": "152",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "399",
"end_idx": "403",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "518",
"end_idx": "522",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "773",
"end_idx": "777",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "902",
"end_idx": "912",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "1112",
"end_idx": "1116",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1228",
"end_idx": "1232",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1371",
"end_idx": "1375",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1395",
"end_idx": "1405",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
},
{
"begin_idx": "1545",
"end_idx": "1549",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
},
{
"begin_idx": "1611",
"end_idx": "1615",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "CDH1"
}
] |
{
"begin_idx": "9",
"end_idx": "19",
"entity_id": "999",
"entity_type": "Gene",
"text_name": "E-cadherin"
}
|
{
"begin_idx": "1686",
"end_idx": "1716",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "gastric and colorectal cancers"
}
|
Yes
|
10075388
|
Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration.
|
In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.
|
Reduced /"bcl-2"/ concentrations in /"hypertensive"/ patients after lisinopril or nifedipine administration.
|
In 30 patients with essential /"hypertension"/ and 30 healthy control subjects, we evaluated blood concentrations of /"B cell leukemia-2"/ (/"bcl-2"/), a protooncogene that can reduce apoptosis. /"Bcl-2"/ concentrations were higher in /"hypertensive"/ than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood /"bcl-2"/ concentrations, in both /"hypertensive"/ and normotensive subjects. Treatment of /"hypertensive"/ patients with hypotensive drugs caused a reduction in /"bcl-2"/ concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of /"bcl-2"/ are increased in patients with /"hypertension"/, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing /"bcl-2"/ concentrations, with potentially beneficial effects on vascular modifications in patients with /"hypertension"/.
|
[
{
"begin_idx": "32",
"end_idx": "44",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "131",
"end_idx": "143",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "320",
"end_idx": "332",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "481",
"end_idx": "493",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "534",
"end_idx": "546",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "780",
"end_idx": "792",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "1070",
"end_idx": "1082",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "561",
"end_idx": "572",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotensive"
},
{
"begin_idx": "8",
"end_idx": "13",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "214",
"end_idx": "231",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "B cell leukemia-2"
},
{
"begin_idx": "233",
"end_idx": "238",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "451",
"end_idx": "456",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "601",
"end_idx": "606",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "743",
"end_idx": "748",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "969",
"end_idx": "974",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "862",
"end_idx": "898",
"entity_id": "D066253",
"entity_type": "Disease",
"text_name": "posthypertensive vascular remodeling"
},
{
"begin_idx": "8",
"end_idx": "13",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "214",
"end_idx": "231",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "B cell leukemia-2"
},
{
"begin_idx": "233",
"end_idx": "238",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "284",
"end_idx": "289",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "Bcl-2"
},
{
"begin_idx": "451",
"end_idx": "456",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "601",
"end_idx": "606",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "743",
"end_idx": "748",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "969",
"end_idx": "974",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
}
] |
{
"begin_idx": "214",
"end_idx": "231",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "B cell leukemia-2"
}
|
{
"begin_idx": "32",
"end_idx": "44",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
}
|
Yes
|
10075388
|
Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration.
|
In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.
|
Reduced /"bcl-2"/-2"/ concentrations in hypertensive patients after lisinopril or nifedipine administration.
|
In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of /"B cell leukemia-2"/-2"/ (/"bcl-2"/-2"/), a protooncogene that can reduce apoptosis. /"Bcl-2"/ concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood /"bcl-2"/-2"/ concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in /"bcl-2"/-2"/ concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of /"bcl-2"/-2"/ are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing /"bcl-2"/-2"/ concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.
|
[
{
"begin_idx": "32",
"end_idx": "44",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "131",
"end_idx": "143",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "320",
"end_idx": "332",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "481",
"end_idx": "493",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "534",
"end_idx": "546",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensive"
},
{
"begin_idx": "780",
"end_idx": "792",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "1070",
"end_idx": "1082",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertension"
},
{
"begin_idx": "561",
"end_idx": "572",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotensive"
},
{
"begin_idx": "8",
"end_idx": "13",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "214",
"end_idx": "231",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "B cell leukemia-2"
},
{
"begin_idx": "233",
"end_idx": "238",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "451",
"end_idx": "456",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "601",
"end_idx": "606",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "743",
"end_idx": "748",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "969",
"end_idx": "974",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
},
{
"begin_idx": "862",
"end_idx": "898",
"entity_id": "D066253",
"entity_type": "Disease",
"text_name": "posthypertensive vascular remodeling"
},
{
"begin_idx": "8",
"end_idx": "13",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "214",
"end_idx": "231",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "B cell leukemia-2"
},
{
"begin_idx": "233",
"end_idx": "238",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "284",
"end_idx": "289",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "Bcl-2"
},
{
"begin_idx": "451",
"end_idx": "456",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "601",
"end_idx": "606",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "743",
"end_idx": "748",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
},
{
"begin_idx": "969",
"end_idx": "974",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
}
] |
{
"begin_idx": "601",
"end_idx": "606",
"entity_id": "596",
"entity_type": "Gene",
"text_name": "bcl-2"
}
|
{
"begin_idx": "743",
"end_idx": "748",
"entity_id": "D015448",
"entity_type": "Disease",
"text_name": "bcl-2"
}
|
No
|
End of preview. Expand
in Data Studio
README.md exists but content is empty.
- Downloads last month
- 10