title: Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing.
abstract: The genetic heterogeneity of congenital hearing disorders makes molecular diagnosis expensive and time-consuming using conventional techniques such as Sanger sequencing of DNA. In order to design an appropriate strategy of molecular diagnosis in the Algerian population, we explored the diversity of the involved mutations by studying 65 families affected by autosomal recessive forms of nonsyndromic hearing impairment (DFNB forms), which are the most prevalent early onset forms. We first carried out a systematic screening for mutations in GJB2 and the recurrent p.(Arg34*) mutation in TMC1, which were found in 31 (47.7%) families and 1 (1.5%) family, respectively. We then performed whole exome sequencing in nine of the remaining families, and identified the causative mutations in all the patients analyzed, either in the homozygous state (eight families) or in the compound heterozygous state (one family): (c.709C>T: p.(Arg237*)) and (c.2122C>T: p.(Arg708*)) in OTOF, (c.1334T>G: p.(Leu445Trp)) in SLC26A4, (c.764T>A: p.(Met255Lys)) in GIPC3, (c.518T>A: p.(Cys173Ser)) in LHFPL5, (c.5336T>C: p.(Leu1779Pro)) in MYO15A, (c.1807G>T: p.(Val603Phe)) in OTOA, (c.6080dup: p.(Asn2027Lys*9)) in PTPRQ, and (c.6017del: p.(Gly2006Alafs*13); c.7188_7189ins14: p.(Val2397Leufs*2)) in GPR98. Notably, 7 of these 10 mutations affecting 8 different genes had not been reported previously. These results highlight for the first time the genetic heterogeneity of the early onset forms of nonsyndromic deafness in Algerian families.
authors.affiliation: Equipe de Génétique, Laboratoire de Biologie Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB) Alger, Algeria.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ammar-Khodja
authors.affiliation: Institut de la Vision, UMRS 1120 INSERM/UPMC/Institut Pasteur Paris, France.
authors.forename: Crystel
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: Equipe de Génétique, Laboratoire de Biologie Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB) Alger, Algeria.
authors.forename: Malika
authors.initials: M
authors.lastname: Dahmani
authors.affiliation: Service d'Otorhinolaryngologie (ORL), Hôpital de Kouba-Bachir Mentouri Alger, Algeria.
authors.forename: Sofiane
authors.initials: S
authors.lastname: Ouhab
authors.affiliation: Institut de la Vision, UMRS 1120 INSERM/UPMC/Institut Pasteur Paris, France.
authors.forename: Gaelle M
authors.initials: GM
authors.lastname: Lefèvre
authors.affiliation: Service d'Otorhinolaryngologie (ORL), Hôpital Mustapha Pacha Alger, Algeria.
authors.forename: Hassina
authors.initials: H
authors.lastname: Ibrahim
authors.affiliation: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition UMRS 1120 INSERM/UPMC Paris 6, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.affiliation: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition UMRS 1120 INSERM/UPMC Paris 6, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.affiliation: Service de Biochimie, Hôpital Armand Trousseau UMRS 1120 INSERM, Paris, France.
authors.forename: Malek
authors.initials: M
authors.lastname: Louha
authors.affiliation: Institut de la Vision, UMRS 1120 INSERM/UPMC/Institut Pasteur Paris, France ; Institut Pasteur, Unité de Génétique et Physiologie de l'Audition UMRS 1120 INSERM/UPMC Paris 6, Paris, France ; Collège de France Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
keywords: Algeria; deafness; genetic heterogeneity; whole exome sequencing