Applying molecular technique in early detection of Wilson asymptomatic patients and carriers

Abstract

Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, which leads to copper deposits in the liver and other organs. This study aimed to identify Wilson asymptomatic patients and carriers in their families. Forty-three WD patients and their 67 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7Bgene were analysed by direct sequencing. We recognised 18 different mutations, accounting for 91.9 %. Mutation S105X was determined to have the highest rate (34.9%) in this study. The hotspot regions of ATP7B were found at exons 2 (40.7%), exon 16 (11.6%), exon 8 (9.3%), intron 14 (7%), and exon 18 (5.9%). Among 11 homozygote/compound heterozygote siblings of the patients with WD, 4 (6%) individuals were determined as asymptomatic by screening mutations of the probands. In conclusion, 18 different mutations were detected. Of this number, mutation S105X is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD. Exons 2, 8, 16, and 18, and intron 14 should be screened initially for WD patients in Vietnam. Four asymptomatic Wilson patients were identified by screening mutations of proband would be treated soon and so far are healthy. Based on risk profile for WD, genetic testing is also useful for asymptomatic diagnosis and treatment.