Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease

被引:408
作者
Hu, ZL
Bonifas, JM
Beech, J
Bench, G
Shigihara, T
Ogawa, H
Ikeda, S
Mauro, T
Epstein, EH [1 ]
机构
[1] San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94110 USA
[2] Univ Calif San Francisco, Dept Dermatol, VA Med Ctr, San Francisco, CA 94143 USA
[3] Univ Calif Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94550 USA
[4] Juntendo Univ, Sch Med, Dept Dermatol, Tokyo 113, Japan
关键词
D O I
10.1038/71701
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Hailey-Hailey disease (HHD, MIM 16960) is inherited in an autosomal dominant manner and characterized by persistent blisters and erosions of the skin(1). Impaired intercellular adhesion and epidermal blistering also occur in individuals with pemphigus (which is due to autoantibodies directed against desmosomal proteins) and in patients with Darier disease (DD, MIM 124200), which is caused by mutations in a gene encoding a sarco/endoplasmic reticulum (ER)-Golgi calcium pump(2). We report here the identification of mutations in ATP2C1, encoding the human homologue of an ATP-powered pump that sequesters calcium into the Golgi in yeast, in 21 HHD kindreds. Regulation of cytoplasmic calcium is impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient is attenuated in vivo in HHD patients. Our findings not only provide an understanding of the molecular basis of HHD, but also underscore the importance of calcium control to the functioning of stratified squamous epithelia.
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页码:61 / 65
页数:5
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