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Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype–phenotype correlation in Indian patients

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Title Molecular pathogenesis of Wilson disease: haplotype analysis, detection
of prevalent mutations and genotype–phenotype correlation in Indian
patients
 
Creator Gupta, A
Aikath, D
Neogi, R
Datta, S
Basu, K
Maity, B
Trivedi, R
Ray, J
Das, S. K
Gangopadhyay, P. K
Ray, Kunal
 
Subject Molecular & Human Genetics
 
Description Wilson disease (WD) is an autosomal recessive
disorder caused by defects in the copper-transporting Ptype
ATPase gene (ATP7B) resulting in the accumulation
of copper in the liver and the brain. We identified
prevalent mutations in the ATP7B of Indian WD patients
and attempted to correlate those with the disease
phenotype. Patients from 62 unrelated families and their
first-degree relatives comprising 200 individuals were
enrolled in this study. Three dinucleotide repeat markers
flanking WD locus and a few intragenic SNPs were used
to determine the genotypes and construct haplotypes of
the patients. Seven recurring haplotypes accounting for
58% of the total mutant chromosomes were identified,
and four underlying defects in the ATP7B representing
37% of WD chromosomes were detected. In addition,
five other rare mutations were characterized. Thus a
total of nine mutations including five novel changes were
identified in the ATP7B of WD patients. Interestingly,
homozygotes for different mutations that would be expected
to produce similar defective proteins showed
significant disparity in terms of organ involvement and
severity of the disease. We also observed WD patients
with neurological symptoms with little or no manifestation of hepatic pathogenesis. In one WD family, the
proband and a sib had remarkably different phenotypes
despite sharing the same pair of mutant chromosomes.
These findings suggest a potential role for yet unidentified
modifying loci for the observed phenotypic heterogeneity
among the WD patients.
 
Date 2005
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/315/1/fuHUMAN_GENETICS__Volume_118_(1)_49%2D57_2005[18].pdf
Gupta, A and Aikath, D and Neogi, R and Datta, S and Basu, K and Maity, B and Trivedi, R and Ray, J and Das, S. K and Gangopadhyay, P. K and Ray, Kunal (2005) Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype–phenotype correlation in Indian patients. Human Genetics, 118. pp. 49-57.
 
Relation http://dx.doi.org/10.1007/s00439-005-0007-y
http://www.eprints.iicb.res.in/315/