Molecular pathogenesis of Wilson disease among Indians: A perspective on mutation spectrum in ATP7B gene, prevalent defects, clinical heterogeneity and implication towards diagnosis

Arnab Gupta, Ishita Chattopadhyay, Sumit Dey, Poonam Nasipuri, Shyamal K. Das, Prasanta K. Gangopadhyay, Kunal Ray

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: We aim to identify the molecular defects in the ATP7B, the causal gene for Wilson disease (WD), in eastern Indian patients and attempt to assess the overall mutation spectrum in India for detection of mutant allele for diagnostic purposes. Methods: Patients from 109 unrelated families and their first-degree relatives comprising 400 individuals were enrolled in this study as part of an ongoing project. Genomic DNA was prepared from the peripheral blood of Indian WD patients. PCR was done to amplify the exons and flanking regions of the WD gene followed by sequencing, to identify the nucleotide variants. Results: In addition to previous reports, we recently identified eight mutations including three novel (c.3412 + 1G > A, c.1771 G > A, c.3091 A > G) variants, and identified patients with variable phenotype despite similar mutation background suggesting potential role of modifier locus. Conclusions: So far we have identified 17 mutations in eastern India including five common mutations that account for 44% of patients. Comparative study on WD mutations between different regions of India suggests high genetic heterogeneity and the absence of a single or a limited number of common founder mutations. Genotype-phenotype correlation revealed that no particular phenotype could be assigned to a particular mutation and even same set of mutations in different patients showed different phenotypes.

Original languageEnglish (US)
Pages (from-to)1023-1033
Number of pages11
JournalCellular and molecular neurobiology
Volume27
Issue number8
DOIs
StatePublished - Dec 1 2007

Keywords

  • ATP7B
  • K-F ring
  • SNP
  • WD
  • Wilson Disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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