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

Autor: Marwa, Sayeb, Zied, Riahi, Nadia, Laroussi, Crystel, Bonnet, Lilia, Romdhane, Rahma, Mkaouar, Anissa, Zaouak, Jihene, Marrakchi, Ghaith, Abdessalem, Olfa, Messaoud, Oussema, Bouchniba, Nacer, Ghilane, Mourad, Mokni, Ghazi, Besbes, Houda, Yacoub-Youssef, Christine, Petit, Sonia, Abdelhak
Přispěvatelé: Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, Hôpital Habib Thameur, Hôpital La Rabta [Tunis], Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Génétique et Physiologie de l'Audition, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), This work was supported by the Tunisian Ministry of Public Health, the Ministry of Higher Education and Scientific Research (LR11IPT05), the E.C. Grant agreement N° 295097 for FP7 project GM‐NCD‐Inco (www.genomedika.org)., We thank the patient and his family for their collaboration. We are grateful to the technical staff at Armand Trousseau Hospital in Paris for their assistance., European Project: 295097,EC:FP7:INCO,FP7-INCO-2011-6,GM_NCD_IN_CO(2011), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Collège de France - Chaire Génétique et physiologie cellulaire
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Dermatology
International Journal of Dermatology, Wiley-Blackwell, 2019, 58 (12), pp.1439-1443. ⟨10.1111/ijd.14452⟩
International Journal of Dermatology, 2019, 58 (12), pp.1439-1443. ⟨10.1111/ijd.14452⟩
ISSN: 0011-9059
DOI: 10.1111/ijd.14452⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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