caa a22 4500 463254619 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10571-007-9192-7 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9192-7 Molecular Pathogenesis of Wilson Disease Among Indians: A Perspective on Mutation Spectrum in ATP7B gene, Prevalent Defects, Clinical Heterogeneity and Implication Towards Diagnosis [Elektronische Daten] [Arnab Gupta, Ishita Chattopadhyay, Sumit Dey, Poonam Nasipuri, Shyamal Das, Prasanta Gangopadhyay, Kunal Ray] 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. Springer Science+Business Media, LLC, 2007 WD nationallicence Wilson Disease nationallicence K-F ring nationallicence SNP nationallicence ATP7B nationallicence Gupta Arnab Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut Chattopadhyay Ishita Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut Dey Sumit Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut Nasipuri Poonam Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut Das Shyamal Bangur Institute of Neuroscience and Psychiatry, Kolkata, India aut Gangopadhyay Prasanta Bangur Institute of Neuroscience and Psychiatry, Kolkata, India aut Ray Kunal Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1023-1033 0272-4340 27:8<1023 2007 27 10571 https://doi.org/10.1007/s10571-007-9192-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9192-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gupta Arnab Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut NATIONALLICENCE 700 1- Chattopadhyay Ishita Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut NATIONALLICENCE 700 1- Dey Sumit Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut NATIONALLICENCE 700 1- Nasipuri Poonam Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut NATIONALLICENCE 700 1- Das Shyamal Bangur Institute of Neuroscience and Psychiatry, Kolkata, India aut NATIONALLICENCE 700 1- Gangopadhyay Prasanta Bangur Institute of Neuroscience and Psychiatry, Kolkata, India aut NATIONALLICENCE 700 1- Ray Kunal Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Jadavpur, 700 032, Kolkata, India aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1023-1033 0272-4340 27:8<1023 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer