Detection And Analysis Of Mutations In Patients With Wilson Disease

Background Wilson's disease(WD) is an autosomal recessive disorder characterized by decreased biliary copper excretion and reduced copper incorporation into ceruloplasmin. The defective biliary excretion leads to accumulation of copper in the liver with progressive liver damage and overflow to other organs, such as brain, cornea and renal. The disease gene ATP7B maps to chromosome 13q14.3,contains 21 exons, and encodes a copper-transporting P-type ATPase.ATP7B mutations are scattered over the entire gene, and more than 200 mutations have been detected up-to-now.Objective To determine mutation characters and distribution of ATP7B gene in Chinese and explore importance and methods of gene diagnosis for WD patient. The genotype and phenotype correlation in patients with WD were also studied.Method 35 individuals, 13patients(9 male and 4 female) from 12 no kinship WD families were enrolled in this study. The age of onset ranged from 5-13 years. Genomic DNA from patients was subjected to polymerase chain reactions (PCR) for exons 5, 8 and 12 of ATP7B gene. PCR products were analyzed by single strand configuration polymorphism (SSCP), denaturing high-performance liquid chromatography (DHPLC) and by direct sequencing.Results Eleven of 13patients had present with hepatic manifestation, 9 of them had only hepatic manifestation, one had hepatic and neurological...