A Tunisian family with a novel mutation in the gene CYP 4F22 for lamellar ichthyosis and co‐occurrence of hearing loss in a child due to mutation in the SLC 26A4 gene

Marwa Sayeb (1) , Zied Riahi (1, 2) , Nadia Laroussi (1) , Crystel Bonnet (2) , Lilia Romdhane (1, 3) , Rahma Mkaouar (1) , Anissa Zaouak (4) , Jihene Marrakchi (5) , Ghaith Abdessalem (1) , Olfa Messaoud (1) , Oussema Bouchniba (6) , Nacer Ghilane (6) , Mourad Mokni (5) , Ghazi Besbes (5) , Houda Yacoub-Youssef (1) , Christine Petit (7, 2, 8) , Sonia Abdelhak (1)

1 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
2 Institut de la Vision
3 Faculté des Sciences de Bizerte [Université de Carthage]
4 Hôpital Habib Thameur
5 Hôpital La Rabta [Tunis]
6 Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax]
7 Génétique et Physiologie de l'Audition
8 Collège de France - Chaire Génétique et physiologie cellulaire

Background: Co-occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations. Methods: We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis-ichthyosis-deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method). Results: The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale-Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively. Conclusions: The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co-occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.

Domains: Life Sciences [q-bio]

Marwa Sayeb, Zied Riahi, Nadia Laroussi, Crystel Bonnet, Lilia Romdhane, et al.. A Tunisian family with a novel mutation in the gene CYP 4F22 for lamellar ichthyosis and co‐occurrence of hearing loss in a child due to mutation in the SLC 26A4 gene. International Journal of Dermatology, 2019, 58 (12), pp.1439-1443. ⟨10.1111/ijd.14452⟩. ⟨pasteur-03219630⟩