title: Whole exome sequencing identifies new causative mutations in Tunisian families with non-syndromic deafness.
abstract: Identification of the causative mutations in patients affected by autosomal recessive non syndromic deafness (DFNB forms), is demanding due to genetic heterogeneity. After the exclusion of GJB2 mutations and other mutations previously reported in Tunisian deaf patients, we performed whole exome sequencing in patients affected with severe to profound deafness, from four unrelated consanguineous Tunisian families. Four biallelic non previously reported mutations were identified in three different genes: a nonsense mutation, c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and TMC1 respectively. We thereby provide evidence that whole exome sequencing is a powerful, cost-effective screening tool to identify mutations causing recessive deafness in consanguineous families.
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia; Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors.forename: Zied
authors.initials: Z
authors.lastname: Riahi
authors.affiliation: INSERM UMRS 1120, Institut de la Vision, Paris, France.
authors.forename: Crystel
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: Service d'ORL et de Chirurgie Maxillo-faciale, CHU La Rabta, Tunis, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Zainine
authors.affiliation: Centre de Référence des Surdités Génétiques, Hôpital Trousseau- APHP, Paris, France.
authors.forename: Malek
authors.initials: M
authors.lastname: Louha
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouyacoub
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia; Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Laroussi
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Chargui
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.affiliation: Centre de Référence des Surdités Génétiques, Hôpital Trousseau- APHP, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Jonard
authors.affiliation: INSERM U931, Clermont Ferrand, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Dorboz
authors.affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur de Paris, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.affiliation: Service d'ORL et de Chirurgie Maxillo-faciale, CHU La Rabta, Tunis, Tunisia.
authors.forename: Sihem Belhaj
authors.initials: SB
authors.lastname: Salah
authors.affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur de Paris, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Levilliers
authors.affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur de Paris, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.affiliation: Unité de Génétique du Développement Humain, Institut Pasteur de Paris, Paris, France.
authors.forename: Kenneth
authors.initials: K
authors.lastname: McElreavey
authors.affiliation: INSERM U931, Clermont Ferrand, France.
authors.forename: Odile Tanguy
authors.initials: OT
authors.lastname: Boespflug
authors.affiliation: Service d'ORL et de Chirurgie Maxillo-faciale, CHU La Rabta, Tunis, Tunisia.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Besbes
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Tunis, Tunisia; Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: INSERM UMRS 1120, Institut de la Vision, Paris, France; Unité de Génétique et Physiologie de l'Audition, Institut Pasteur de Paris, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26