title: Recessive TBC1D24 Mutations Are Frequent in Moroccan Non-Syndromic Hearing Loss Pedigrees.
abstract: Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Amina
authors.initials: A
authors.lastname: Bakhchane
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco; Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier, BP 74103, 34091 Montpellier cedex 05, France; PREMMi, Mitochondrial Medicine Research Centre, Université d'Angers, CHU Bât IRIS/IBS, Rue des Capucins, 49933 Angers cedex 9, France.
authors.forename: Majida
authors.initials: M
authors.lastname: Charif
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco; Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier, BP 74103, 34091 Montpellier cedex 05, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Salime
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Redouane
authors.initials: R
authors.lastname: Boulouiz
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Halima
authors.initials: H
authors.lastname: Nahili
authors.affiliation: Université Hassan II Ain Chock, Laboratoire de Physiologie et génétique moléculaire, Km 8 Route d'El Jadida, B.P 5366 Maarif, Casablanca, 20100, Morocco.
authors.forename: Rachida
authors.initials: R
authors.lastname: Roky
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier, BP 74103, 34091 Montpellier cedex 05, France; PREMMi, Mitochondrial Medicine Research Centre, Université d'Angers, CHU Bât IRIS/IBS, Rue des Capucins, 49933 Angers cedex 9, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lenaers
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Barakat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003638:Deafness / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009018:Morocco; D059645:Mutation Rate; D009419:Nerve Tissue Proteins; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human