Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.
Hum Mol Genet 1992 May
PMID:The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. 130 Nov 61

Waardenburg syndrome type 1 (WS1) is an autosomal dominant disorder characterized by deafness, dystopia canthorum, heterochromia iridis, white forelock, and premature greying. A similar phenotype is caused in the mouse by mutations in the Pax-3 gene. This observation, together with comparisons of conserved syntenies in the murine and human genetic maps, suggested that at least some WS1 mutations should occur in HuP2, the probable human homolog of Pax-3. Two mutations in the HuP2 sequence of individuals with WS1 have been reported recently. Both of them occur in the highly conserved paired box region of the gene, which encodes a DNA binding domain. The functional consequences of these mutations are at present speculative. We report here a 14 bp deletion in the paired domain encoded by exon 2 of HuP2 in an Indonesian family segregating for WS1. This frameshift mutation results in a premature termination codon in exon 3. The HuP2 product is a truncated protein lacking most of the paired domain and all of the predicted homeo domain. We propose that the WS1 phenotype in this family is due to loss of function of HuP2 and discuss two mechanisms for the dominant effect of this mutation.
Hum Mol Genet 1992 Jul
PMID:A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. 130 93

Alport syndrome is a mainly X-linked hereditary disease of basement membranes characterized by progressive renal failure, deafness, and ocular lesions. The alpha 3(IV) and alpha 4(IV) collagen genes have been recently shown to be involved in the less frequent autosomal recessive form. When screening lymphocyte COL4A3 mRNAs from Alport patients, we found a mutant whose transcripts were disrupted by a 74 bp insertion at the junction of exons IV or V and VI. The insertion derives from an antisense Alu element in COL4A3 intron V, which has been spliced into the alpha 3(IV) mRNA due to a G to T transversion activating a cryptic acceptor splice site in this Alu element. There is complete segregation of this mutation with the disease in the family. Our findings provide the first evidence for the pathogenic role of abnormal splicing of COL4A3. Moreover, we demonstrate the superiority of mutation screening at the mRNA level to detect a hitherto poorly recognized mutation mechanism in humans, splice-mediated insertion of an Alu fragment into a coding sequence.
Hum Mol Genet 1995 Apr
PMID:Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal recessive Alport syndrome. 763 17

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most common cause of congenital bowel obstruction with an incidence of 1 in 5000 live births. Recently, linkage of an incompletely penetrant, dominant form of HSCR was reported, followed by identification of mutations in the RET receptor tyrosine kinase. To determine the frequency of RET mutations in HSCR and correlate genotype with phenotype, we have screened for mutations among 80 HSCR probands representing a wide range of phenotypes and family structures. Polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis of RET's 20 exons for mutations among probands revealed eight putative mutations (10%). Sequence changes, which included missense, frameshift and complex mutations, were detected in both familial and isolated cases, among patients with both long- and short-segment HSCR and in three kindreds with other phenotypes (maternal deafness, talipes and malrotation of the gut, respectively). Two mutations (C609Y and C620R) we identified have previously been associated with multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC) and, on rare occasions, HSCR. Thus, while HSCR family members may be at risk for developing neuroendocrine tumors, it follows that identical mutations in RET may be able to participate in the pathogenesis of distinct phenotypes. Our data suggest that: (i) the overall frequency of RET mutations in HSCR patients is low and therefore, other genetic and/or environmental determinants contribute to the majority of HSCR susceptibility, and (ii) at present, there is no obvious relationship between RET genotype and HSCR phenotype.
Hum Mol Genet 1995 May
PMID:Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. 763 41

Genotypes for 53 short tandem repeat (STR) markers distributed at an average of 39 cM intervals throughout the genome were determined for 46 individuals from the village of Bengkala, Bali. This village of approximately 2200 individuals has an oral and written tradition suggesting genetic bottlenecks. The allele frequency distributions in Bengkala were compared with distributions obtained by typing individuals in the CEPH data base using a Kolmogorov-Smirnov two sample test. Twenty-eight of the 53 markers showed differences (P < 0.05) in distribution between the two populations. Allele frequencies of tetranucleotide STRs were much more similar between the two populations than were those of dinucleotide STRs (P < 0.043). Population heterogeneity in Bengkala was indicated by an excess of observed homozygosity, deviations from Hardy-Weinberg equilibrium at seven loci, and significant allelic associations between physically unlinked loci. In addition to providing information pertinent to the issue of genetic diversity of STRs in the human population, these analyses serve as a resource to map a gene causing non-syndromal autosomal recessive deafness in Bengkala, and to corroborate the anthropological study of the history and social structure of the village.
Hum Mol Genet 1995 Jan
PMID:Analysis of short tandem repeat (STR) allele frequency distributions in a Balinese population. 771 38

Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals.
Environ Mol Mutagen 1995
PMID:Influence of heredity on human sensitivity to environmental chemicals. 778 56

Genetic deafness is relatively common, accounting for about half of the 1 in 1000 children born with a significant hearing impairment. Heterogeneity is a particular problem when searching for genes for deafness in humans, and the mouse may prove to be a valuable model not only for investigating the nature of the deafness once the gene is known, but also for finding the gene by positional cloning. Several genes causing syndromic deafness have been identified in humans, but the largest group in the population have autosomal recessive deafness, and identification of homologous genes in the mouse may be the only route to these genes. Progress with positional cloning of the shaker-1 mouse mutation is described.
Hum Mol Genet 1994
PMID:Genetic deafness--progress with mouse models. 784 37

The first localization of a gene responsible for autosomal, neurosensory, recessive deafness recently assigned NSRD1 to the centromeric region of human chromosome 13. We now report on a dominant form of neurosensory deafness found in a family of French origin. The deafness is moderate to severe, has a prelingual onset and affects predominantly the high frequencies. The gene responsible for this form of deafness was found by linkage analysis to map to the same region of chromosome 13 as NSRD1. A multipoint analysis gave a maximum lod score of 4.66 with a most likely location close to locus D13S175. This suggests that different mutations in NSRD1 may cause both dominant and recessive neurosensory deafness.
Hum Mol Genet 1994 Dec
PMID:A gene responsible for a dominant form of neurosensory non-syndromic deafness maps to the NSRD1 recessive deafness gene interval. 788 23

The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage analysis of a highly consanguineous family. A maximum lod score of 10.63 (theta = 0.018) was obtained for the microsatellite marker D11S527. Homozygosity mapping refined the localization of NSRD2 to a 6 cM interval also containing the olfactory marker protein (OMP) gene. The murine homologue of OMP is tightly linked to the autosomal recessive deafness gene sh-1. These results, and clinical data, suggest that NSRD2 is the human homologue of the mouse sh-1 gene.
Hum Mol Genet 1994 Jun
PMID:A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. 795 Dec 50

We have found that the microsatellite marker AFM207zg5 (DXS995) maps to all previously described deletions which are associated with X-linked mixed deafness (DFN3) with or without choroideremia and mental retardation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were used to construct a complete 850 kb cosmid contig. Cosmids from this contig have been tested by Southern blot analysis on DNA from 16 unrelated males with X-linked deafness. Two novel microdeletions were detected in patients which exhibit the characteristic DFN3 phenotype. Both deletions are completely contained within one of the known DFN3-deletions, but one of them does not overlap with two previously described deletions in patients with contiguous gene syndromes consisting of DFN3, choroideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal region of at least 400 kb.
Hum Mol Genet 1994 Jul
PMID:X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions. 798 85


1 2 3 4 5 6 7 8 9 10 Next >>