title: Molecular pathogenesis of Wilson disease among Indians: a perspective on mutation spectrum in ATP7B gene, prevalent defects, clinical heterogeneity and implication towards diagnosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700 032, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Gupta
authors.forename: Ishita
authors.initials: I
authors.lastname: Chattopadhyay
authors.forename: Sumit
authors.initials: S
authors.lastname: Dey
authors.forename: Poonam
authors.initials: P
authors.lastname: Nasipuri
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Das
authors.forename: Prasanta K
authors.initials: PK
authors.lastname: Gangopadhyay
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005190:Family; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D017386:Sequence Homology, Amino Acid