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Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease

Sawicka, J. and Kutkowska-Kaźmierczak, A. and Woźniak, Krzysztof and Tysarowski, A. and Osipowicz, K. and Poznański, Jarosław and Rygiel, A. M. and Braun-Walicka, N. and Niepokój, K. and Bal, Jerzy and Kowalewski, C. and Wertheim-Tysarowska, K. (2020) Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease. Journal of Applied Genetics, 61 (2). pp. 187-193. ISSN 1234-1983


Official URL: http://doi.org/10.1007/s13353-020-00538-8


Hailey-Hailey disease (HHD) is a rare, late-onset autosomal dominant genodermatosis characterized by blisters, vesicular lesions,crusted erosions, and erythematous scaly plaques predominantly in intertriginous regions. HHD is caused by ATP2C1 mutations. About 180 distinct mutations have been identified so far; however, data of only few cases from Central Europe are available. The aim was to analyze the ATP2C1 gene in a cohort of Polish HHD patients. A group of 18 patients was enrolled in the study based on specific clinical symptoms. Mutations were detected using Sanger or next generation sequencing. In silico analysis was performed by prediction algorisms and dynamic structural modeling. In two cases, mRNA analysis was performed to confirm aberrant splicing. We detected 13 different mutations, including 8 novel, 2 recurrent (p.Gly850Ter and c.325-3 T > G), and 6 sporadic (c.423-1G > T, c.899 + 1G > A, p.Leu539Pro, p.Thr808TyrfsTer16, p.Gln855Arg and a complex allele: c.[1610C >G;1741 + 3A > G]). In silico analysis shows that all novel missense variants are pathogenic or likely pathogenic. We confirmed pathogenic status for two novel variants c.325-3 T > G and c.[1610C > G;1741 + 3A > G] by mRNA analysis. Our results broaden the knowledge about genetic heterogeneity in Central European patients with ATP2C1 mutations and also give further evidence that careful and multifactorial evaluation of variant pathogenicity status is essential.

Item Type:Article
Subjects:Q Science > Q Science (General)
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
Divisions:Department of Biophysics
ID Code:1880
Deposited By: Prof Jaroslaw Poznanski
Deposited On:15 May 2020 13:28
Last Modified:15 May 2020 13:28

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