1. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations
- Author
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Sebastien Albert, Pierre Bitoun, Christine Francannet, Françoise Denoyelle, Bruno Delobel, Didier Lacombe, Marie-Madeleine Eliot, Annie Sergent-Allaoui, Hélène Dollfus, Sébastien Schmerber, Alain Joannard, Pierre Chauvin, Muriel Houang, Valérie Drouin-Garraud, N. Loundon, Albert David, Erea-Noel Garabedian, Catherine Calais, Françoise Duriez, Rémy Couderc, Hélène Blons, Delphine Feldmann, Laurence Jonard, Christine Petit, Marie-Françoise Obstoy, Hélène Catros, Sandrine Marlin, Patrice Tran Ba Huy, Jacques Leman, Hubert Journel, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique des Déficits Sensoriels, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Service d'ORL et de chirurgie cervicale, CHU Grenoble, CHU Saint-Antoine [AP-HP], Centre Rochin, Unité de Génétique Médicale, CHR Vannes, Centre Gabriel Deshayes, Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'ORL et chirurgie cervico-faciale, Service d'oto-rhino-laryngologie (ORL), Hôtel-Dieu, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'ORL, chirurgie cervico-faciale [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service d'oto-rhino-laryngologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'ORL, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôtel-Dieu-CHU Clermont-Ferrand, Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Service d'ORL pédiatrique et Chirurgie Cervico-faciale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Chaire Génétique et physiologie cellulaire, Service de génétique et embryologie médicales [CHU Trousseau], Chauvin, Pierre, Neurobiologie des réseaux sensorimoteurs (NRS (U7060)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des réseaux sensorimoteurs ( NRS (U7060) ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), and Magnani, Christophe
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Male ,Pediatrics ,Vestibular aqueduct ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Deafness ,Connexins ,MESH: Membrane Transport Proteins ,Cohort Studies ,0302 clinical medicine ,MESH: Child ,Prevalence ,Medicine ,Nonsyndromic deafness ,Child ,030223 otorhinolaryngology ,MESH: Cohort Studies ,Genetics (clinical) ,Pendred syndrome ,Genetics ,Goiter ,Homozygote ,Syndrome ,MESH: European Continental Ancestry Group ,MESH: Infant ,Connexin 26 ,medicine.anatomical_structure ,Sulfate Transporters ,[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Sensorineural hearing loss ,medicine.symptom ,MESH: Homozygote ,Adult ,medicine.medical_specialty ,MESH: Mutation ,Adolescent ,Hearing loss ,Hearing Loss, Sensorineural ,MESH: Deafness ,MESH: Goiter ,White People ,Vestibular Aqueduct ,03 medical and health sciences ,otorhinolaryngologic diseases ,Humans ,Alleles ,MESH: Prevalence ,MESH: Adolescent ,MESH: Humans ,business.industry ,MESH: Alleles ,MESH: Child, Preschool ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Infant ,Membrane Transport Proteins ,Congenital sensorineural hearing impairment ,MESH: Adult ,medicine.disease ,MESH: Male ,MESH: Connexins ,FOXI1 ,MESH: Hearing Loss, Sensorineural ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Mutation ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,sense organs ,business ,MESH: Female ,Enlarged vestibular aqueduct - Abstract
Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.
- Published
- 2006
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