REP-1 gene mutations in Japanese patients with choroideremia

Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patie nts with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-I gene. In the present study, we performed ex tensive analysis of the REP-I gene in patients with CHM from several instit utions in Japan. Methods: Twenty-six patients with CHM and 5 unaffected fem ales from 22 independently ascertained families were examined. Exons 1-15 o f the REP-I gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. Resu lts: Fifteen different mutations, including one previously reported mutatio n, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. Conclusions: Fifteen different mutations of the REP-I gene were detected in 18 Japanese families. There were no hot spots for the mutations and no mis sense mutations. The results show that REP-1 gene defects cause CHM in Japa nese patients, and the mutations in these Japanese patients differed from t he mutations reported for CHM patients in Europe, Canada, and America excep t for R267X and 1313delTC. These findings suggest that the mutations occurr ed independently in the Japanese patients.