Heterogeneous mutations of the ATP2C1 gene causing Hailey–Hailey disease in Hong Kong Chinese.

Background Hailey–Hailey disease (HHD) is a rare autosomal dominant dermatosis. It causes suprabasilar acantholysis leading to vesicular and crusted erosions affecting the flexures. Mutation of ATP2C1 gene encoding the human secretory pathway Ca2+/Mn2+-ATPase (hSPCA1) was identified to be the cause of this entity. Objective The aim of this study was to study the mutational profile of the ATP2C1 gene in Hong Kong Chinese patients with HHD. Methods Patients with the clinical diagnosis of HHD proven by skin biopsy were included in this study. Mutation analysis was performed in 17 Hong Kong Chinese patients with HHD. Results Ten mutations in the ATP2C1 gene were found. Six of these were novel mutations. The novel mutations included a donor splice site mutation (IVS22+1G>A); a missense mutation (c.1049A>T); two deletion mutations (c.185_188delAGTT and c.923_925delAAG); an acceptor splice site mutation (IVS21-1G>C) and an insertion mutation (c.2454dupT). Conclusion The six novel mutations provide additions to the HHD mutation database. No hot-spot mutation was found and high allelic heterogeneity was demonstrated in the Hong Kong Chinese patients. [ABSTRACT FROM AUTHOR]