Two novel mutations in the ATP2C1 gene found in Japanese patients with Hailey-Hailey disease

Abstract

Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis and the defective gene in HHD is ATP2C1, which encodes secretory pathway Ca²⁺ /Mn²⁺ ATPase type 1 (SPCA1). Here we report four Japanese HHD patients showing three kinds of mutations with premature termination codons in the ATP2C1 gene, including two novel ones. Patient 1 was a 39-year-old man with a novel heterozygous mutation, c.664dup in exon 8 (p.N215Kfs*26). Patient 2 was a 33-year-old man (the younger brother of patient 1) with the same mutation as patient 1. Patient 3 was a 55-year-old man with a previously reported heterozygous mutation, c.519dup in exon 7 (p.R174Tfs*4). Patient 4 was a 33-year-old woman with a novel heterozygous mutation, c.2640del in exon 27 (p.L881Ffs*10). The clinical characteristics of our four cases varied in disease severity and the response to treatment. The present cases enrich the database of mutational analysis for HHD.

Keywords: ATP2C1; Hailey-Hailey disease; Japanese; novel mutation; premature termination codons.