The Role of the ATP2C1 Gene in Hailey-Hailey Disease

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2017 May 29

PMID 28551824

Citations 22

Authors

Hao Deng

Heng Xiao

Affiliations

Soon will be listed here.

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 Ca/Mn by transporting Ca/Mn into the Golgi apparatus. ATP2C1 gene mutations are reportedly responsible for abnormal cytosolic Ca/Mn 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.

Citing Articles

Hailey-Hailey Disease Successfully Treated With Adalimumab: A Case Series.

Alicea-Negron A, Gonzalez-Barreto R, Gonzalez-Chavez J Cureus. 2024; 16(8):e67227.

PMID: 39295647 PMC: 11410359. DOI: 10.7759/cureus.67227.

Late-onset Hailey-Hailey disease with a novel ATP2C1 mutation in an older female patient.

Horikawa T, Yamaguchi S, Omine T, Miyagi T, Utsumi D, Takahashi K JAAD Case Rep. 2024; 50:91-93.

PMID: 39070920 PMC: 11279969. DOI: 10.1016/j.jdcr.2023.11.036.

A novel ATP2C1 mutation (c.1840-1G>A) in a sporadic case of isolated perianal Hailey-Hailey disease with human papillomavirus type 58 infection.

Zhu Y, Fan Y, Cai Y, Chen Y, Qiu F An Bras Dermatol. 2024; 99(4):601-603.

PMID: 38637183 PMC: 11221149. DOI: 10.1016/j.abd.2022.12.011.

Focus on pemphigus treatment publications: A bibliometric and visual analysis (1992-2022).

Wang X, Huang C, Li W, Hong Y Heliyon. 2024; 10(7):e28462.

PMID: 38590872 PMC: 10999929. DOI: 10.1016/j.heliyon.2024.e28462.

Hailey-Hailey disease exacerbated by scabies: the role of dermatoscopy in preventing misdiagnosis.

Zychowska M, Kolt-Kaminska M, Kijowski R, Reich A Postepy Dermatol Alergol. 2023; 40(4):567-570.

PMID: 37692273 PMC: 10485762. DOI: 10.5114/ada.2023.130477.

References

Kellermayer R . Hailey-Hailey disease as an orthodisease of PMR1 deficiency in Saccharomyces cerevisiae. FEBS Lett. 2005; 579(10):2021-5. DOI: 10.1016/j.febslet.2005.03.003. View

Dhitavat J, Fairclough R, Hovnanian A, Burge S . Calcium pumps and keratinocytes: lessons from Darier's disease and Hailey-Hailey disease. Br J Dermatol. 2004; 150(5):821-8. DOI: 10.1111/j.1365-2133.2004.05904.x. View

Engin B, Kutlubay Z, Celik U, Serdaroglu S, Tuzun Y . Hailey-Hailey disease: A fold (intertriginous) dermatosis. Clin Dermatol. 2015; 33(4):452-5. DOI: 10.1016/j.clindermatol.2015.04.006. View

Ramos-Castaneda J, Park Y, Liu M, Hauser K, Rudolph H, Shull G . Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress. J Biol Chem. 2004; 280(10):9467-73. PMC: 2527542. DOI: 10.1074/jbc.M413243200. View

Jahangir A, Ozcan C, Holmuhamedov E, Terzic A . Increased calcium vulnerability of senescent cardiac mitochondria: protective role for a mitochondrial potassium channel opener. Mech Ageing Dev. 2001; 122(10):1073-86. DOI: 10.1016/s0047-6374(01)00242-1. View

Happle R . The categories of cutaneous mosaicism: A proposed classification. Am J Med Genet A. 2015; 170A(2):452-459. DOI: 10.1002/ajmg.a.37439. View

Maclennan D, RICE W, Green N . The mechanism of Ca2+ transport by sarco(endo)plasmic reticulum Ca2+-ATPases. J Biol Chem. 1997; 272(46):28815-8. DOI: 10.1074/jbc.272.46.28815. View

Sudbrak R, Brown J, Dobson-Stone C, Carter S, Ramser J, White J . Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca(2+) pump. Hum Mol Genet. 2000; 9(7):1131-40. DOI: 10.1093/hmg/9.7.1131. View

Btadini W, Abou Hassan O, Saadeh D, Abbas O, Ballout F, Kibbi A . Identification of several mutations in ATP2C1 in Lebanese families: insight into the pathogenesis of Hailey-Hailey disease. PLoS One. 2015; 10(2):e0115530. PMC: 4319924. DOI: 10.1371/journal.pone.0115530. View

10.

Van Baelen K, Dode L, Vanoevelen J, Callewaert G, De Smedt H, Missiaen L . The Ca2+/Mn2+ pumps in the Golgi apparatus. Biochim Biophys Acta. 2004; 1742(1-3):103-12. DOI: 10.1016/j.bbamcr.2004.08.018. View

11.

Amagai M, Kobayashi M, Wakabayashi K, Hakuno M, Hashiguchi A, Nishikawa T . A case of generalized Hailey-Hailey disease with fatal liver injury. Keio J Med. 2001; 50(2):109-16. View

12.

Folster-Holst R, Nellen R, Jensen J, Poblete-Gutierrez P, Steijlen P, Schwarz T . Molecular genetic support for the rule of dichotomy in type 2 segmental Darier disease. Br J Dermatol. 2011; 166(2):464-6. DOI: 10.1111/j.1365-2133.2011.10593.x. View

13.

Leinonen P, Myllyla R, Hagg P, Tuukkanen J, Koivunen J, Peltonen S . Keratinocytes cultured from patients with Hailey-Hailey disease and Darier disease display distinct patterns of calcium regulation. Br J Dermatol. 2005; 153(1):113-7. DOI: 10.1111/j.1365-2133.2005.06623.x. View

14.

Burge S, Wilkinson J . Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol. 1992; 27(1):40-50. DOI: 10.1016/0190-9622(92)70154-8. View

15.

Hu Z, Bonifas J, Beech J, Bench G, Shigihara T, Ogawa H . Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet. 1999; 24(1):61-5. DOI: 10.1038/71701. View

16.

Callewaert G, Parys J, De Smedt H, Raeymaekers L, Wuytack F, Vanoevelen J . Similar Ca(2+)-signaling properties in keratinocytes and in COS-1 cells overexpressing the secretory-pathway Ca(2+)-ATPase SPCA1. Cell Calcium. 2003; 34(2):157-62. DOI: 10.1016/s0143-4160(03)00070-8. View

17.

WILGRAM G, CAULFIELD J, Lever W . An electron-microscopic study of acantholysis and dyskeratosis in Hailey's disease. J Invest Dermatol. 1962; 39:373-81. View

18.

Ton V, Rao R . Expression of Hailey-Hailey disease mutations in yeast. J Invest Dermatol. 2004; 123(6):1192-4. DOI: 10.1111/j.0022-202X.2004.23437.x. View

19.

Iino Y, Kano T, Adachi F, Suzuki M, Nishikawa R, Ishii N . A case of bullous pemphigoid associated with psoriasis vulgaris showing Hailey-Hailey disease-like histopathological changes in regenerated epidermis without genomic mutation in ATP2C1 or ATP2A2 gene. J Eur Acad Dermatol Venereol. 2014; 29(8):1646-8. DOI: 10.1111/jdv.12521. View

20.

Okunade G, Miller M, Azhar M, Andringa A, Sanford L, Doetschman T . Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes Golgi stress, apoptosis, and midgestational death in homozygous embryos and squamous cell tumors in adult heterozygotes. J Biol Chem. 2007; 282(36):26517-27. DOI: 10.1074/jbc.M703029200. View