{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:46:41Z","timestamp":1762508801148,"version":"3.40.5"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","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":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autosomal recessive congenital ichthyosis (ARCI) refers to a large and genetically heterogenous group of non\u2010syndromic disorders of cornification featuring diffuse scaling. Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome is a rare autosomal recessive syndromic form of ichthyosis. The disease usually results from premature termination codon\u2010causing pathogenic variants in <jats:italic>CLDN1<\/jats:italic> encoding CLAUDIN\u20101 (CLDN1). We used whole exome sequencing (WES), Sanger sequencing, 3D protein modeling, Western blotting, and immunofluorescence confocal microscopy to delineate the genetic basis of ichthyosis in two siblings with ichthyosis but no other ectodermal abnormalities. One of the two siblings underwent liver transplantation in early childhood due to biliary atresia. Both patients were found to carry a homozygous missense pathogenic variant, c.242G&gt;A (p.Arg81His), in <jats:italic>CLDN1<\/jats:italic>. The variant resulted in decreased CLDN1 expression in patient skin. 3D protein modeling predicted that p.Arg81His induces deleterious conformational changes. Accordingly, HaCaT cells transfected with a construct expressing the mutant <jats:italic>CLDN1<\/jats:italic> cDNA featured decreased levels and mislocation of CLDN1 as compared with cells expressing the wildtype cDNA. In conclusion, we describe the first pathogenic missense variant in <jats:italic>CLDN1<\/jats:italic> shown to result in ARCI.<\/jats:p>","DOI":"10.1002\/ajmg.a.62924","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T10:43:58Z","timestamp":1659523438000},"page":"2879-2887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in <i>CLDN1<\/i>"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-7566","authenticated-orcid":false,"given":"Janan","family":"Mohamad","sequence":"first","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5387-5490","authenticated-orcid":false,"given":"Liat","family":"Samuelov","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5574-4918","authenticated-orcid":false,"given":"Sari","family":"Assaf","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-7761","authenticated-orcid":false,"given":"Liron","family":"Malki","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-6668","authenticated-orcid":false,"given":"Kiril","family":"Malovitski","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odile","family":"Meijers","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-8409","authenticated-orcid":false,"given":"Noam","family":"Adir","sequence":"additional","affiliation":[{"name":"Schulich Faculty of Chemistry, Technion  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Granot","sequence":"additional","affiliation":[{"name":"Shoham Medical Center  Pardes Hana Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-4739","authenticated-orcid":false,"given":"Mor","family":"Pavlovsky","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-2091","authenticated-orcid":false,"given":"Ofer","family":"Sarig","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4093-1032","authenticated-orcid":false,"given":"Eli","family":"Sprecher","sequence":"additional","affiliation":[{"name":"Division of Dermatology Tel Aviv Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21326"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3522"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01809.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.023887"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.08.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58718-9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.040"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.09.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02262-08"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05654"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20333"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24761"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.07.022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.71"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.05.007"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12724"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006897"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/508617"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34407"},{"issue":"5","key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.jhep.2020.07.006","article-title":"NISCH syndrome: An extremely rare cause of neonatal cholestasis","volume":"73","journal-title":"Journal of Hepatology"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0794-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.01.009"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.04.032"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.02.030"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2010.1192"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15996"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.09794.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21674"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"volume-title":"GeneReviews","year":"2001","author":"Richard G.","key":"e_1_2_9_32_1"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030825"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","unstructured":"Salik D. Hadj\u2010Rabia S. Hohl D. Vahidnezhad H. Youssefian L. Rakosi A. Dangoisse C. Marangoni M. Vilain C. & Smits G. (2022).Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome.Pediatric Dermatology.https:\/\/doi.org\/10.1111\/pde.14976","DOI":"10.1111\/pde.14976"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.14569"},{"issue":"6","key":"e_1_2_9_36_1","first-page":"L647","article-title":"Structure, function, and regulation of cellular tight junctions","volume":"262","author":"Schneeberger E. E.","year":"1992","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","unstructured":"Szepetowski S. Lacoste C. Mallet S. Roquelaure B. Badens C. & Fabre A. (2017).Le syndrome NISCH une cause rare de cholestase n\u00e9onatale: \u00e0 propos d\u2019un cas. Archives de P\u00e9diatrie 24(12) 1228\u20131234.https:\/\/doi.org\/10.1016\/j.arcped.2017.09.016","DOI":"10.1016\/j.arcped.2017.09.016"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908929116"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.595593"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00200-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.533"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2007.00624.x"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62924","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:43:42Z","timestamp":1708497822000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/ajmg.a.62924"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62924","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"assertion":[{"value":"2022-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}