Mutation Analysis of the ATP7B Gene in Seven Chinese Families with Wilson's Disease

Background: Wilson's disease (WD) is an autosomal recessive disease, which is characterized by an excessive copper accumulation in the liver and brain, leading to subsequent hepatic and/or neurological disorders. The causative gene for WD has been identified as the ATPase Cu2+ transporting beta polypeptide gene (ATP7B), which encodes a protein called copper- transporting ATPase 2. ATP7B mutations may lead to reduced biliary excretion of excess copper and disrupted copper homeostasis, resulting in various clinical symptoms of WD. Methods: Direct sequencing of the ATP7B gene was performed in 7 Han Chinese families with WD, and haplotype analysis was conducted in families having the same mutation. Results: Nine ATP7B gene mutations were identified, including 7 missense mutations (p. Asp765Gly, p. Arg778Leu, p. Thr888Pro, p. Pro992Leu, p.Asp1047Val, p. Ile1148Thr and p. Ala1295Val), 1 duplication mutation (c. 525dupA), and 1 nonsense mutation (p. Gly837*). Combined with our previous data, haplotype analysis revealed that the founder effect accounted for 48% of alleles in Han Chinese, constituted by high allele frequency mutations p. Arg778Leu, p. Pro992Leu and p. Ala1295Val. Conclusion: This study revealed genetic defects of 7 Han Chinese families with WD, and has implications for their genetic counseling and clinical management. (C) 2018 S. Karger AG, Basel