ABSTRACT
PURPOSE: Wilson disease is an autosomal recessive disorder which causes excessive copper accumulation in the hepatic region. So far, ATP7B gene is the only disease-causing gene of Wilson disease known to date. However, ATP7B mutations have not been found in ~15% of the patients. This study was performed to identify any causative gene in Wilson disease patients without an ATP7B mutation in either allele. MATERIALS AND METHODS: The sequence of the coding regions and exon-intron boundaries of the five ATP7B-interacting genes, ATOX1, COMMD1, GLRX, DCTN4, and ZBTB16, were analyzed in the 12 patients with Wilson disease. RESULTS: Three nonsynonymous variants including c.1084A>G (p.Thr362Ala) in the exon 12 of the DCTN4 gene were identified in the patients examined. Among these, only p.Thr362Ala was predicted as possibly damaging protein function by in silico analysis. Examination of allele frequency of c.1084A>G (p.Thr362Ala) variant in the 176 patients with Wilson disease and in the 414 normal subjects revealed that the variant was more prevalent in the Wilson disease patients (odds ratio [OR]=3.14, 95% confidence interval=1.36-7.22, P=0.0094). CONCLUSION: Our result suggests that c.1084A>G (p.Thr362Ala) in the ATP7B-interacting DCTN4 gene may be associated with the pathogenesis of Wilson disease.