Mutational analysis of ATP7B and genotype - Phenotype correlation in Japanese with Wilson's disease

The gene ATP7B responsible for Wilson's disease (WD) produces a protein whi ch is predicted to be a copper binding P-type ATPase, homologous to the Men kes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect disease causing mutations, to clarify their freq uency and distribution, to determine whether genotype correlates with pheno type, and to determine the rate of abnormal findings in heterozygotes for t he WD gene. We analyzed 41 unrelated Japanese WD families, including 47 pat ients. Twenty-one mutations, including nine novel ones, were identified. 28 71delC (15.9%), 1708-5T-->G (11.0%), and Arg778Leu (13.4%) were the most co mmon mutations. 2871delC was detected mainly in eastern Japan and 1708-5T-- >G in western Japan. The homozygotes for the 1708-5T-->G, 2871delC, or Arg7 78Leu mutations did not show a correlation with their phenotypes. Cerulopla smin and copper levels were abnormally low in 28.6% and 35.0% of heterozygo tes, respectively. When patients and their families are screened for WD, a high rate of abnormal laboratory data in heterozygotes must be taken into a ccount Hum Mutat 15:454-462, 2000. (C) 2000 Wiley-Liss, Inc.