Molecular Pathogenesis of Wilson Disease: Haplotype Analysis, Detection of Prevalent Mutations and Genotype–Phenotype Correlation in Indian Patients
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| 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 Maiti, B Trivedi, R Roy, J Das, S K Gangopadhyay, Prasanta K Roy, 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 identi.ed
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
.rst-degree relatives comprising 200 individuals were
enrolled in this study. Three dinucleotide repeat markers
.anking 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 identi.ed,
and four underlying defects in the ATP7B representing
37% of WD chromosomes were detected. In addition,
.ve other rare mutations were characterized. Thus a
total of nine mutations including .ve novel changes were
identi.ed in the ATP7B of WD patients. Interestingly,
homozygotes for di.erent mutations that would be expected
to produce similar defective proteins showed
signi.cant 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 di.erent phenotypes
despite sharing the same pair of mutant chromosomes.
These .ndings suggest a potential role for yet unidenti-
.ed 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/1112/1/HUMAN_GENETICS%2C_118(_1)%2C_49%2D57_[18].pdf
Gupta, A and Aikath, D and Neogi, R and Datta, S and Basu, K and Maiti, B and Trivedi, R and Roy, J and Das, S K and Gangopadhyay, Prasanta K and Roy, Kunal (2005) Molecular Pathogenesis of Wilson Disease: Haplotype Analysis, Detection of Prevalent Mutations and Genotype–Phenotype Correlation in Indian Patients. Human Genetics, 118 (1). pp. 49-57. |
|
| Relation |
http://dx.doi.org/10.1007/s00439-005-0007-y
http://www.eprints.iicb.res.in/1112/ |
|