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Genetic analysis of ATP7B in 102 south Indian families with Wilson disease.

Authors :
Nivedita Singh
Pradeep Kallollimath
Mohd Hussain Shah
Saketh Kapoor
Vishwanath Kumble Bhat
Lakshminarayanapuram Gopal Viswanathan
Madhu Nagappa
Parayil S Bindu
Arun B Taly
Sanjib Sinha
Arun Kumar
Source :
PLoS ONE, Vol 14, Iss 5, p e0215779 (2019)
Publication Year :
2019
Publisher :
Public Library of Science (PLoS), 2019.

Abstract

Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ATP7B. We report here the genetic analysis of 102 WD families from a south Indian population. Thirty-six different ATP7B mutations, including 13 novel ones [p.Ala58fs*19, p.Lys74fs*9, p.Gln281*, p.Pro350fs*12, p.Ser481*, p.Leu735Arg, p.Val752Gly, p.Asn812fs*2, p.Val845Ala, p.His889Pro, p.Ile1184fs*1, p.Val1307Glu and p.Ala1339Pro], were identified in 76/102 families. Interestingly, the mutation analysis of affected individuals in two families identified two different homozygous mutations in each family, and thus each affected individual from these families harbored two mutations in each ATP7B allele. Of 36 mutations, 28 were missense, thus making them the most prevalent mutations identified in the present study. Nonsense, insertion and deletion represented 3/36, 2/36 and 3/36 mutations, respectively. The haplotype analysis suggested founder effects for all the 14 recurrent mutations. Our study thus expands the mutational landscape of ATP7B with a total number of 758 mutations. The mutations identified during the present study will facilitate carrier and pre-symptomatic detection, and prenatal genetic diagnosis in affected families.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
14
Issue :
5
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.81a5e7e58da43aa88d12f5f5c36f15d
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0215779