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The role of the ATP2C1 gene in Hailey–Hailey disease

Cellular and Molecular Life Sciences volume 74, pages 3687–3696 (2017)Cite this article

Abstract

Hailey–Hailey disease (HHD) is a rare autosomal dominant acantholytic dermatosis, characterized by a chronic course of repeated and exacerbated skin lesions in friction regions. The pathogenic gene of HHD was reported to be the ATPase calcium-transporting type 2C member 1 gene (ATP2C1) located on chromosome 3q21–q24. Its function is to maintain normal intracellular concentrations of Ca2+/Mn2+ by transporting Ca2+/Mn2+ into the Golgi apparatus. ATP2C1 gene mutations are reportedly responsible for abnormal cytosolic Ca2+/Mn2+ levels and the clinical manifestations of HHD. Environmental factors and genetic modifiers may also affect the clinical variability of HHD. This article aims to critically discuss the clinical and pathological features of HHD, differential diagnoses, and genetic and functional studies of the ATP2C1 gene in HHD. Further understanding the role of the ATP2C1 gene in the pathogenesis of HHD by genetic, molecular, and animal studies may contribute to a better clinical diagnosis and provide new strategies for the treatment and prevention of HHD.

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Fig. 1
Fig. 2

Abbreviations

A :

Actuator domain

ASTE1:

Asteroid homolog 1

ATP:

Adenosine triphosphate

ATP2C1:

ATPase calcium–transporting type 2C member 1

C. elegans :

Caenorhabditis elegans

DD:

Darier disease

HHD:

Hailey–Hailey disease

M:

Transmembrane

N:

Nucleotide–binding domain

P:

Phosphorylation domain

PTCs:

Premature termination codons

PV:

Pemphigus vulgaris

SERCA:

Sarcoplasmic/endoplasmic reticulum Ca2+–ATPase

SPCA:

Secretory pathway Ca2+/Mn2+–ATPase

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Acknowledgements

This work was supported by grants from the National Key Research and Development Program of China (2016YFC1306604), the National Natural Science Foundation of China (81670216), the Natural Science Foundation of Hunan Province (2015JJ4088 and 2016JJ2166), the grant for the Foster Key Subject of the Third Xiangya Hospital of Central South University (Clinical Laboratory Diagnostics), and the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University (20150301), China.

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  1. Hao Deng and Heng Xiao contributed equally to this work.

Affiliations

  1. Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, 410013, Hunan, People’s Republic of China

    Hao Deng & Heng Xiao

  2. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People’s Republic of China

    Hao Deng

  3. Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People’s Republic of China

    Heng Xiao

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  1. Hao Deng
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  2. Heng Xiao
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Correspondence to Hao Deng.

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Deng, H., Xiao, H. The role of the ATP2C1 gene in Hailey–Hailey disease. Cell. Mol. Life Sci. 74, 3687–3696 (2017). https://doi.org/10.1007/s00018-017-2544-7

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  • DOI: https://doi.org/10.1007/s00018-017-2544-7

Keywords

  • Clinical manifestation
  • Gene function
  • Genetics
  • Mutation analysis
  • Pathogenesis
  • Animal model