Molecular epidemiology of non‐syndromic autosomal recessive congenital ichthyosis in a Middle‐Eastern population

Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a rare and heterogeneous skin cornification disorder presenting with generalized scaling and varying degrees of erythema. 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-exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotypephenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI-associated genes including TGM1 (21%), CYP4F22 (18%), ALOX12B (14%), ABCA12 (10%), ALOXE3 (6%), NIPAL4 (5%), PNPLA1 (3%), LIPN (2%) and SDR9C7 (2%). In 19% of cases, no | 1291 MOHAMAD et Al.

Identification of the first congenital ichthyosis case caused by a homozygous deletion in the ALOX12B gene due to chromosome 17 mixed uniparental disomy

“…The search terms included the combination of the following groups of keywords: 1) “ ALOX12B gene,” or “Arachidonate 12-Lipoxygenase”; 2) “variant” or “mutation”; and 3) “recessive congenital ichthyosis” or “self-improving collodion ichthyosis.” The initial electronic search identified 90 articles in PubMed, 46 in Scopus, 92 in Embase, and 77 in Web of Science. After removing the duplicates and screening the articles by title and abstract, we discarded 281 articles, and 24 remained ( Jobard et al, 2002 ; Eckl et al, 2005 ; Ashoor et al, 2006 ; Lesueur et al, 2007 ; Harting et al, 2008 ; Eckl et al, 2009 ; Akiyama et al, 2010 ; Kurban et al, 2010 ; Vahlquist et al, 2010 ; Li et al, 2012 ; Chaitidis et al, 2013 ; Israeli et al, 2013 ; Osorio et al, 2013 ; Numata et al, 2015 ; Lolas et al, 2016 ; Bastaki et al, 2017 ; Alavi et al, 2020 ; Fioretti et al, 2020 ; Anker et al, 2021 ; Frommherz et al, 2021 ; Hotz et al, 2021 ; Mohamad et al, 2021 ; Srinivas et al, 2021 ). Mutations in the ALOX12B gene were described according to the Human Genome Variation Society, using the NCBI reference sequence NM_001139.3.…”

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

“…Various pure and compound heterozygous mutations in the PNPLA1 gene have been identified from a registry of human ichthyosis patients. To date, approximately 59 pathogenic mutations in the PNPLA1 gene have been reported ( Table 1 ) [ 2 , 4 , 24 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. These mutations include 35 missense mutations, four code-shifting mutations, eight nonsense mutations, four deletion mutations, three splice-site mutations, two early termination mutations, and one full code mutation.…”

Congenital Ichthyosis: Clinical and Genetic Characteristics of the Disease

“…Высокой генетической и клинической гетерогенностью отличается ARCI [8,9]. Основная подгруппа ARCIихтиоз Арлекина, ламеллярный ихтиоз и врожденная ихтиозиформная эритродермия [10][11][12]. Клинически они характеризуются шелушением, гиперкератозом, вариабельной эритродермией, часто -наличием коллодиевой мембраны при рождении, а также эктропионом и кератодермией при более тяжелых формах.…”

“…Например, J. Mohamad и соавт. [11] изучали когорту из 91 пациента -арабского происхождения, друзов и евреев. Была выявлена более высокая распространенность патогенных вариантов генов CYP4F22 и ABCA12 и более низкая -TGM1 и NIPAL4 по сравнению с распределением этих вариантов в других популяциях.…”