Identification Of Novel ATP2C1 Mutations In Patients With Hailey-Hailey Disease

Background Familial benign chronic pemphigus or Hailey-Hailey disease (HHD; OMIM 169600) is a rare autosomal dominant cutaneous disorder characterized by recurrent vesicles and erosions mainly in intertriginous areas. It was first described by the brothers Hailey in 1939. The disease usually presents in the third or fourth decade and the lesions occur mainly on the neck and intertriginous areas; mucosal involvement is rare, but has been seen in the mouth, esophagus, and vulva. Asymptomatic longitudinal white lines on the fingernails are seen in some patients. Lesions are induced or exacerbated by external factors such as sweating, friction, and cutaneous infection. Histologic examination shows numerous acantholytic cells and the suprabasal type of blister formation, ultrastructural studies of acantholytic cells in HHD reveal perinuclear aggregates of keratin intermediate filaments that have retracted from desmosomal plaques. Linkage analysis mapped the gene responsible for HHD to chromosome 3q21-q24. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding the human secretory pathway calcium ATPase1(hSPCA1). A spectrum of missense, frameshift, splice-site, and nonsense mutations have since been reported in ATP2C1. Comparison between genotype and phenotype failed to yield any clear correlation between the nature of the mutation and the clinical features of HHD. In the present study, we have ascertained two Chinese families with HHD, and examined ATP2C1 gene mutations in these two families by direct sequencing. Objectives To identify pathogenic mutations of the ATP2C1 gene in two Chinese...