{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:57:51Z","timestamp":1791536271935,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin\u20101. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in\n                    <jats:italic>CLDN1<\/jats:italic>\n                    , a single missense variant CLDN1 p.Arg81His, associated with isolated skin ichthyosis phenotype, has been recently reported in a family of Moroccan Jewish descent. We now describe seven patients with ILVASC, originating from four non consanguineous families of North African Jewish ancestry (including one previously reported family), harboring CLDN1 p.Arg81His variant, and broaden the phenotypic spectrum attributed to this variant to include teeth, hair, and liver\/bile duct involvement, characteristic of ILVASC. Furthermore, we provide additional evidence for pathogenicity of the CLDN1 p.Arg81His variant by transmission electron microscopy of the affected skin, revealing distorted tight junction architecture, and show through haplotype analysis in the vicinity of the\n                    <jats:italic>CLDN1<\/jats:italic>\n                    gene, that this variant represents a founder variant in Jews of Moroccan descent with an estimated carrier frequency of 1:220.\n                  <\/jats:p>","DOI":"10.1111\/cge.14432","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T22:38:06Z","timestamp":1697063886000},"page":"44-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews"],"prefix":"10.1111","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-1505","authenticated-orcid":false,"given":"Marina","family":"Eskin\u2010Schwartz","sequence":"first","affiliation":[{"name":"Soroka University Medical Center Genetics Institute  Beer\u2010Sheva Israel"},{"name":"Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Dolgin","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Center for Rare Diseases, Faculty of Health Sciences and National Institute for Biotechnology in the Negev Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Didkovsky","sequence":"additional","affiliation":[{"name":"Rabin Medical Center Institute of Pathology  Petah Tiqwa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Aminov","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Center for Rare Diseases, Faculty of Health Sciences and National Institute for Biotechnology in the Negev Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pikovsky","sequence":"additional","affiliation":[{"name":"Oral Medicine Unit, Department of Oral and Maxillofacial Surgery Soroka University Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Hadar","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Center for Rare Diseases, Faculty of Health Sciences and National Institute for Biotechnology in the Negev Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Kristal","sequence":"additional","affiliation":[{"name":"Saban Pediatric Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Ling","sequence":"additional","affiliation":[{"name":"Saban Pediatric Medical Center  Beer\u2010Sheva Israel"},{"name":"Pediatric Gastroenterology Unit  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idan","family":"Cohen","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Zilberman","sequence":"additional","affiliation":[{"name":"Pediatric Dental Unit Barzilai Medical Center  Ashkelon 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