{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:45Z","timestamp":1753861785357,"version":"3.41.2"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010983","name":"Health Research Fund of Central Denmark Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006286","name":"Kongelig Hofbuntmager Aage Bangs Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hailey\u2010Hailey disease (OMIM#169600) is an autosomal dominantly inherited genodermatosis characterized by erosions in the flexural areas of the body. Hailey\u2010Hailey disease is caused by variants in <jats:italic>ATP2C1<\/jats:italic>, but for ~10% of the patients, no causative variant is found in the coding region of <jats:italic>ATP2C1<\/jats:italic>. We aimed to determine the genetic cause of Hailey\u2010Hailey disease in a family without a variant in the coding areas of <jats:italic>ATP2C1<\/jats:italic>. By genome sequencing and analysis of all exon and intron sequences of <jats:italic>ATP2C1<\/jats:italic>, we identified the variant c.532\u2010560 T&gt;G (NM_014382.5) in intron 7 of <jats:italic>ATP2C1<\/jats:italic>. The variant is predicted by <jats:italic>in silico<\/jats:italic> tools to create a new deep intronic donor splice site. Segregation analysis detected the variant in the three affected family members. RNA sequencing confirmed that the variant creates a new deep intronic donor splice site that gives rise to an alternative exon. The identified deep\u2010intronic variant in <jats:italic>ATP2C1<\/jats:italic> is the likely cause of Hailey\u2010Hailey disease. This is to our knowledge the first report of a deep\u2010intronic variant as the cause of Hailey\u2010Hailey disease, which shows that the analysis of the intronic sequences of <jats:italic>ATP2C1<\/jats:italic> could increase the genetic diagnostic yield for Hailey\u2010Hailey disease patients.<\/jats:p>","DOI":"10.1002\/ajmg.a.63933","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T07:15:32Z","timestamp":1731309332000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hailey\u2010Hailey Disease Caused by a Novel Deep Intronic Variant in <scp><i>ATP2C1<\/i><\/scp>"],"prefix":"10.1002","volume":"197","author":[{"given":"Jenny","family":"Blechingberg","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorkild","family":"Terkelsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus N Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uffe Birk","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"R\u00f8nholt","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Sommerlund","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne","family":"Vinter","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-8281","authenticated-orcid":false,"given":"Lise","family":"Graversen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12528.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2544-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/71701"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"volume-title":"StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u00a9 2024","year":"2024","author":"Konstantinou M. P.","key":"e_1_2_9_6_1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.381"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S384443"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23164"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703029200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2021.4012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"issue":"10","key":"e_1_2_9_13_1","first-page":"1478","article-title":"Darier and Hailey\u2010Hailey Disease: Update 2021","volume":"19","author":"Rogner D. 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