Abstract: Objective To understand the mutation characteristics and clinical characteristics of ATP7B gene of pedigrees with hepatolenticular degeneration (HLD), which is also called Wilson's Disease (WD), and to explore the relationship between mutation and the pathogenesis of WD.Methods Peripheral blood samples from 5 members of pedigrees with the WD were collected, genomic DNA was extracted, then we analysed the clinical manifestations and mutations.Results All patients in the 5 pedigrees showed liver damage of varying degrees, and even some patients developed liver failure, but no neurological symptoms occurred. Most patients had K-F ring and with decreased serum ceruloplasmin. ATP7B gene detection showed that all the five probands were caused by multiple mutations, while the parents of the probands only carried a single pathogenic mutation gene. Seven pathogenic mutations were detected, including five missense mutations, one nonsense mutations and one insertion mutation, in which c.3087_3088insT (p.G1030Wfs*39) was a new insertion mutation. In addition, 10 single nucleotide polymorphisms were detected. One pre symptomatic patient was diagnosed by family genetic testing.Conclusion In this study, most patients with WD show liver damage, but the clinical symptoms and ages of onset are different. Compound heterozygous mutation is the most popular mutation form of ATP7B, and a novel pathogenic mutation has been identified. Gene sequencing analysis is helpful for rapid diagnosis of pre symptomatic patients in pedigrees with WD.

Key words: Wilson's Disease, ATP7B, Mutation analysis