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The recent availability of whole exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (<jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>) and ichthyosis and was primarily suspected as suffering from keratitis\u2010ichthyosis\u2010deafness (<jats:styled-content style=\"fixed-case\">KID<\/jats:styled-content>) syndrome. <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> was performed for the index case, and all members of the nuclear family were sequenced (Sanger method).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T&gt;G (p.Leu445Trp) in exon 11 of <jats:italic><jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>26A4<\/jats:italic> gene, associated with isolated <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content> and a novel missense mutation c.728G&gt;T (p.Arg243Leu) in exon 8 of <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>4F22<\/jats:italic> gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale\u2010Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content> and ichthyosis, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co\u2010occurrence of two distinct clinical entities. In addition, in countries with limited resources, <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijd.14452","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T08:33:48Z","timestamp":1556181228000},"page":"1439-1443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Tunisian family with a novel mutation in the gene <i><scp>CYP<\/scp>4F22<\/i> for lamellar ichthyosis and co\u2010occurrence of hearing loss in a child due to mutation in the <i><scp>SLC<\/scp>26A4<\/i> gene"],"prefix":"10.1111","volume":"58","author":[{"given":"Marwa","family":"Sayeb","sequence":"first","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05) University of Tunis El Manar Pasteur Institut 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