Eight Novel Mutations of <i>ATP2C1</i> Identified in 17 Chinese Families with Hailey-Hailey Disease

Abstract

Background: Hailey-Hailey disease (HHD) is a rare autosomal dominantly inherited dermatosis, characterized by persistent blisters and erosions of the skin. It was recently discovered that HHD was caused by mutations in the ATP2C1 gene, a Ca²⁺ pump located in the Golgi apparatus. Observation: In this study, we sequenced the ATP2C1 gene from blood samples of 31 patients in 17 unrelated Chinese families and 120 healthy individuals. Eight novel mutations were identified in 9families, including 3 insertion/deletions (nt 1464–1487/1462–1485 del, 1523 del AT, 2375 del TTGT), 3 splicing-site mutations [360(–2)a→g, 1415(–2)a→c, 2243(+2)t→c], and 2 missense mutations (P307L, D648Y). Conclusion: Eight mutations were found in 8 unrelated families and 1 sporadic case, and these new findings have further improved our understanding of the role of ATP2C1 in HHD.

Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease

“…We did not find mutations in 17 patients (24%) with DD and three patients (17%) with HHD, which is similar to figures reported in the literature [Sakuntabhai et al., ; Hu et al., ; Ikeda et al., ; Ringpfeil et al., ; Dobson‐Stone et al., ; Yokota et al., ; Ikeda et al., ; Li et al., ; Zhang et al., ; Hamada et al., ; Bchetnia et al., ; Cheng et al., ; Godic et al., ; Fu et al., ; Klausegger et al., ; Green et al., ; ]. Of interest though, one DD patient showed skipping of exon 4 of ATP2A2 on the mRNA level, which indicates that, for instance, larger deletions or cryptic splice‐site mutations may account for the disease phenotype.…”

Six novel ATP2C1 mutations identified in Chinese patients with Hailey–Hailey disease

“…The protein serves to actively pump Ca 2+ and Mn 2+ across Golgi membranes and control the cations' intracellular homeostasis [4,6]. To date, 111 pathological mutations have been described scattered throughout the ATP2C1 gene with no indication of mutational hotspot or clustering of mutations (Table 1) [4][5][6][7][8][9][10]. In this study, we performed the mutation analysis of the ATP2C1 gene in HHD patients from Shandong Province, PR China and identified six novel mutations.…”

Dermoscopic and reflectance confocal microscopic presentation of Hailey‐Hailey disease: A case series

“…This gene encodes a Ca 2+ /Mn 2+ ATPase which is a calcium pump present on the Golgi apparatus. 3,4 Mutations will result in calcium deposition failure, ending in desmosomal separation, keratinocyte adhesion defects, and acantholysis. 5 Skin lesions usually develop in the second to fourth decades of life, with equal sex incidence.…”