Three novel ATP2C1 mutations in Chinese patients with Hailey-Hailey disease

Hailey-Hailey disease (HHD, OMIM 169600) is a kind of autosomal dominant dermatosis. Hailey-Hailey disease is caused by mutations in the ATPase, Ca2+ transporting, type 2C, member 1 gene (ATP2C1) located at chromosome 3q22.1, encoding for human secretory pathway Ca2+/Mn2+ ATPase protein 1 (hSPCA1) which plays an important role in controlling Ca2+ concentration in the cytoplasm and Golgi apparatus of human keratinocytes [1]. Hailey-Hailey disease patients present with recurrent pruritic vesicles, painful erosions, and scaly erythematous plaques, which are caused by intraepidermal acantholysis due to retraction of keratin filaments from the desmosomal plaque and formation of perinuclear aggregates [2]. The disease most commonly affects intertriginous areas symmetrically such as the neck, axillae, groin, and perineum. Mechanical trauma, ultraviolet radiation, heat, sweating, or infection can cause exacerbations [3]. Here we report three Chinese families with HHD and identified three novel mutations of ATP2C1 sequence variations.
Three Chinese HHD families’ patients, unaffected family members, and 100 unrelated normal individuals were collected for mutation analysis. This study was previously approved by our local ethics committee, the Institutional Ethical Review Boards of the Peking Union Medical College and written informed consent was obtained from all subjects. The proband of family 1 was a 45-year-old woman with a 10-year history of HHD presenting with recurrent erythematous, erosive plaques with fissures. These lesions spread over bilateral axilla, groin and midriff area (Figure 1). Her mother and two sisters had similar lesions in their armpits and groin. The proband of family 2 was a 51-year-old man presenting with recurrent erythematous plaques, vesicles, erosions and crust involving the neck, bilateral axillary and inguinal areas with a 15-year history (Figure 2). The lesions were aggravated by sweating or hot weather. And the lesions flared up when he drank alcohol. His father and sister had similar lesions in their armpits and groin. The proband of family 3 was a 32-year-old man with a 4-year history of typical skin lesions of HHD (Figure 3). His mother had similar lesions in her neck, armpits and groin and midriff area. And all patients were confirmed by the histopathological test.
Genomic DNA samples were extracted from peripheral blood samples of HHD patients, unaffected family members, and 100 unrelated healthy individuals using...


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