Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns

We report herein mutations of ATP2C1 in 11 Japanese patients with Hailey-Hailey disease gene (including five previously reported) and compare the mutation pattern with clinical phenotypes. Patients with missense mutations and some of those with mutations causing premature termination showed erythema and erosions primarily at intertriginous areas. In two families with unique mutations, one with an in-frame three amino acid deletion plus an eight amino acid insertion and one with a two base pair deletion predicted to cause premature truncation, some affected individuals had unique clinical features - generalization of Hailey-Hailey disease and generalized skin eruption resembling keratotic papules in Darier's disease - but other affected individuals did not, suggesting the presence of severe intrafamilial phenotype variations. Our findings suggest that differences in clinical phenotypes are probably related to factors other than the type of causative mutation.