Two novel mutations of the ATP2C1 gene in Chinese families with Hailey–Hailey disease

Abstract

Familial benign chronic pemphigus or Hailey–Hailey disease (HHD; OMIM 169600) is an autosomal dominant cutaneous disorder that typically manifests as recurrent vesicles and erosions mainly in intertriginous areas such as the axillae, groin and neck. External facts such as sweating, friction, and cutaneous infection can cause exacerbation of skin eruptions [ [1] Burge S. Hailey–Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol. 1992; 126: 275-282 Crossref PubMed Scopus (251) Google Scholar ]. 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 [ [2] Wilgram G. Caulfield J. Lever W. An electronmicroscopic study of acantholysis and dyskeratosis in Hailey–Hailey disease. J Invest Dermatol. 1962; 39: 373-381 Crossref PubMed Scopus (56) Google Scholar ]. These observations suggest that molecules which mediate adhesion between keratinocytes might be involved in the loss of cell–cell adhesion in the epidermis. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding the human secretory pathway calcium ATPase1 (hSPCA1) [ 3 Hu Z. Bonifas J.M. Beech J. Bench G. Shigihara T. Ogawa H. et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey–Hailey disease. Nat Genet. 2000; 24: 61-65 Crossref PubMed Scopus (434) Google Scholar , 4 Sudbrak R. Brown J. Dobson-Stone C. Carter S. Ramser J. White J. et al. Hailey–Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump. Hum Mol Genet. 2000; 9: 1131-1140 Crossref PubMed Scopus (255) Google Scholar ].