Related Experiment Videos
Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease
1Department of Dermatology, San Francisco General Hospital, University of California at San Francisco, San Francisco, California, USA.
Nature Genetics
|December 30, 1999
Summary
Hailey-Hailey disease is caused by mutations in the ATP2C1 gene, affecting calcium regulation in skin cells. This discovery clarifies the molecular basis of this blistering skin disorder.
Area of Science:
- Genetics
- Dermatology
- Cell Biology
Background:
- Hailey-Hailey disease (HHD) is an autosomal dominant blistering skin disorder.
- Impaired intercellular adhesion and epidermal blistering are hallmarks of HHD, similar to pemphigus and Darier disease.
- The genetic basis of HHD remained largely unknown.
Purpose of the Study:
- To identify the gene responsible for Hailey-Hailey disease.
- To elucidate the molecular mechanisms underlying HHD pathogenesis.
- To understand the role of calcium regulation in stratified squamous epithelia.
Main Methods:
- Genetic analysis of 21 HHD kindreds.
- Mutation screening of candidate genes, including ATP2C1.
- Analysis of calcium regulation in patient-derived keratinocytes and in vivo skin samples.
Main Results:
- Mutations in ATP2C1 were identified in 21 HHD kindreds.
- ATP2C1 encodes a calcium pump involved in sequestering calcium into the Golgi.
- Impaired cytoplasmic calcium regulation and attenuated epidermal calcium gradient were observed in HHD patients.
Conclusions:
- Mutations in ATP2C1 are the molecular cause of Hailey-Hailey disease.
- Disruption of calcium homeostasis is critical to HHD pathogenesis.
- Calcium regulation is essential for the proper function of stratified squamous epithelia.