{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:53:00Z","timestamp":1780066380756,"version":"3.54.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epidermolytic ichthyosis (EI) is a type of congenital ichthyosis, characterized by erythema and blistering at birth followed by hyperkeratosis. EI is caused by pathogenic variants in the genes <jats:italic>KRT1<\/jats:italic> and <jats:italic>KRT10<\/jats:italic>, encoding the proteins keratin 1 (KRT1) and keratin 10 (KRT10), respectively, and is primarily transmitted by autosomal\u2010dominant inheritance, although recessive inheritance caused by nonsense variants in <jats:italic>KRT10<\/jats:italic> is also described. The keratins form a network of intermediate filaments and are a structural component of the cytoskeleton, giving strength and resilience to the skin. We present three cases of mild EI caused by pathogenic KRT10 variations in the L12 linker domain. To our knowledge, this is the first time L12 linker domain pathogenic variants are identified in <jats:italic>KRT10<\/jats:italic> for EI. The aim of this study was to identify gene variants for patients with EI in <jats:italic>KRT1<\/jats:italic> or <jats:italic>KRT10<\/jats:italic>. To establish the pathogenicity of the found variations in <jats:italic>KRT10<\/jats:italic>, we evaluated all patients and available family members clinically. Genetic analyses were performed using Sanger sequencing. Vectors containing wild\u2010type or mutated forms of <jats:italic>KRT10<\/jats:italic> were transfected into HaCaT cells and analyzed by high\u2010resolution confocal microscopy. Genetic analysis of <jats:italic>KRT10<\/jats:italic> identified a heterozygous de novo variant c.910G&gt;A p.(Val304Met) in family 1, a familial heterozygous variant c.911T&gt;C p.(Val304Ala) in family 2, and a familial heterozygous variant c.917T&gt;C p.(Met306Thr) in family 3. All identified missense variants were located in the L12 linker domain of KRT10. In\u00a0vitro study of aggregate formation of the missense variants in KRT10 only showed a very mild and not quantifiable aggregate formation in the KRT10 network, compared with the wild\u2010type sequence. We report three different novel missense variants in the L12 linker domain of KRT10 in patients with an atypical, milder form of EI resembling peeling skin syndrome.<\/jats:p>","DOI":"10.1111\/1346-8138.17395","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T12:28:14Z","timestamp":1722256094000},"page":"1180-1186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Variants in the L12 linker domain of KRT10 are causal to atypical epidermolytic ichthyosis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-4274","authenticated-orcid":false,"given":"J. J. A. J.","family":"van der Velden","sequence":"first","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-7787","authenticated-orcid":false,"given":"M. W.","family":"van Gisbergen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A. F.","family":"Kamps","sequence":"additional","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-216X","authenticated-orcid":false,"given":"G. F. H.","family":"Diercks","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMCG Center of Expertise for Blistering Diseases University Medical Center Groningen, University of Groningen  Groningen The Netherlands"},{"name":"Department of Pathology, UMCG Center of Expertise for Blistering Diseases University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-0380","authenticated-orcid":false,"given":"P. M.","family":"Steijlen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-8020","authenticated-orcid":false,"given":"M.","family":"van Geel","sequence":"additional","affiliation":[{"name":"Department of Dermatology Maastricht University Medical Centre+  Maastricht The Netherlands"},{"name":"GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"},{"name":"Department of Clinical Genetics Maastricht University Medical Centre+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-9363","authenticated-orcid":false,"given":"M. C.","family":"Bolling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMCG Center of Expertise for Blistering Diseases University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018275"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.284"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-2105-4"},{"key":"e_1_2_7_5_1","volume-title":"StatPearls","author":"Rice AS","year":"2022"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.13324"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.03.1146"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.12.019"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2007.00328.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12534.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-021-00374-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1128"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100741"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1994.01690080092014"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09617.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12786"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00389.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.10146.x"},{"key":"e_1_2_7_19_1","unstructured":"Consortium U.Uniprot. 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