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Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease
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 identi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148260/ https://www.ncbi.nlm.nih.gov/pubmed/31983024 http://dx.doi.org/10.1007/s13353-020-00538-8 |
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author | Sawicka, J. Kutkowska-Kaźmierczak, A. Woźniak, K. Tysarowski, A. Osipowicz, K. Poznański, J. Rygiel, A. M. Braun-Walicka, N. Niepokój, K. Bal, J. Kowalewski, C. Wertheim-Tysarowska, K. |
author_facet | Sawicka, J. Kutkowska-Kaźmierczak, A. Woźniak, K. Tysarowski, A. Osipowicz, K. Poznański, J. Rygiel, A. M. Braun-Walicka, N. Niepokój, K. Bal, J. Kowalewski, C. Wertheim-Tysarowska, K. |
author_sort | Sawicka, J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7148260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-71482602020-04-16 Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease Sawicka, J. Kutkowska-Kaźmierczak, A. Woźniak, K. Tysarowski, A. Osipowicz, K. Poznański, J. Rygiel, A. M. Braun-Walicka, N. Niepokój, K. Bal, J. Kowalewski, C. Wertheim-Tysarowska, K. J Appl Genet Human Genetics • Original Paper 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. Springer Berlin Heidelberg 2020-01-25 2020 /pmc/articles/PMC7148260/ /pubmed/31983024 http://dx.doi.org/10.1007/s13353-020-00538-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Human Genetics • Original Paper Sawicka, J. Kutkowska-Kaźmierczak, A. Woźniak, K. Tysarowski, A. Osipowicz, K. Poznański, J. Rygiel, A. M. Braun-Walicka, N. Niepokój, K. Bal, J. Kowalewski, C. Wertheim-Tysarowska, K. Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title | Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title_full | Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title_fullStr | Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title_full_unstemmed | Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title_short | Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease |
title_sort | novel and recurrent variants of atp2c1 identified in patients with hailey-hailey disease |
topic | Human Genetics • Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148260/ https://www.ncbi.nlm.nih.gov/pubmed/31983024 http://dx.doi.org/10.1007/s13353-020-00538-8 |
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