Novel mutations of the ATP7B gene in Japanese patients with Wilson disease

Wilson disease (WD) is an autosomal recessive disorder characterized by cop per accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By dire ct sequencing, we identified five mutations, of which two were novel, and 1 6 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513de1A shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early o nset, the mutations A874V, R778L, and 3892delGTC were either missense mutat ions or inframe 1-amino acid deletion, and occurred in the patients with he pato-neurologic type of late onset. The mutations 2871delC and R778L have b een previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesi s that the mutations tend to occur in a population-specific manner. Therefo re, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.