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Clinical manifestations range from lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) through the most severe form of ARCI, Harlequin ichthyosis (HI). We used homozygosity mapping, whole\u2010exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotype\u2010phenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI\u2010associated genes including <jats:italic>TGM1<\/jats:italic> (21%), <jats:italic>CYP4F22<\/jats:italic> (18%), <jats:italic>ALOX12B<\/jats:italic> (14%), <jats:italic>ABCA12<\/jats:italic> (10%), <jats:italic>ALOXE3<\/jats:italic> (6%), <jats:italic>NIPAL4<\/jats:italic> (5%), <jats:italic>PNPLA1<\/jats:italic> (3%), <jats:italic>LIPN<\/jats:italic> (2%) <jats:italic>and SDR9C7<\/jats:italic> (2%). In 19% of cases, no mutation was identified. Our cohort revealed a higher prevalence of <jats:italic>CYP4F22<\/jats:italic> and <jats:italic>ABCA12<\/jats:italic> pathogenic variants and a lower prevalence of <jats:italic>TGM1<\/jats:italic> and <jats:italic>NIPAL4<\/jats:italic> variants, as compared to data obtained in other regions of the world. Most variants (89%) in <jats:italic>ALOX12B<\/jats:italic> were associated with CIE and were the most common cause of ARCI among patients of Muslim origin (26%). Palmoplantar keratoderma associated with fissures was exclusively a result of pathogenic variants in <jats:italic>TGM1<\/jats:italic>. To our knowledge, this is the largest cohort study of ARCI in the Middle\u2010Eastern population reported to date. Our data demonstrate the importance of population\u2010tailored mutation screening strategies and shed light upon specific genotype\u2010phenotype correlations.<\/jats:p>","DOI":"10.1111\/exd.14345","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T07:49:45Z","timestamp":1617176985000},"page":"1290-1297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Molecular epidemiology of non\u2010syndromic autosomal recessive congenital ichthyosis in a Middle\u2010Eastern population"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-7566","authenticated-orcid":false,"given":"Janan","family":"Mohamad","sequence":"first","affiliation":[{"name":"Division of Dermatology and Pediatric Dermatology Unit Tel Aviv Sourasky Medical Center Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University Tel Aviv 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