title: Molecular epidemiology of DFNB1 deafness in France.
abstract: BACKGROUND
  Mutations in the GJB2 gene have been established as a major cause of inherited non syndromic deafness in different populations. A high number of sequence variations have been described in the GJB2 gene and the associated pathogenic effects are not always clearly established. The prevalence of a number of mutations is known to be population specific, and therefore population specific testing should be a prerequisite step when molecular diagnosis is offered. Moreover, population studies are needed to determine the contribution of GJB2 variants to deafness. We present our findings from the molecular diagnostic screening of the GJB2 and GJB6 genes over a three year period, together with a population-based study of GJB2 variants.
  
  
  RESULTS
  Molecular studies were performed using denaturing High Performance Liquid Chromatograghy (DHPLC) and sequencing of the GJB2 gene. Over the last 3 years we have studied 159 families presenting sensorineural hearing loss, including 84 with non syndromic, stable, bilateral deafness. Thirty families were genotyped with causative mutations. In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population. Finally, we have compared the prevalence of the variants in the hearing impaired population with the general population.
  
  
  CONCLUSIONS
  Although a high heterogeneity of sequence variation was observed in patients and controls, the 35delG mutation remains the most common pathogenic mutation in our population. Genetic counseling is dependent on the knowledge of the pathogenicity of the mutations and remains difficult in a number of cases. By comparing the sequence variations observed in hearing impaired patients with those sequence variants observed in general population, from the same ethnic background, we show that the M34T, V37I and R127H variants can not be responsible for profound or severe deafness.
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU Montpellier, IURC, Montpellier, France. afroux@igh.cnrs.fr
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Roux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pallares-Ruiz
authors.forename: Anne
authors.initials: A
authors.lastname: Vielle
authors.forename: Valérie
authors.initials: V
authors.lastname: Faugère
authors.forename: Carine
authors.initials: C
authors.lastname: Templin
authors.forename: Dorothée
authors.initials: D
authors.lastname: Leprevost
authors.forename: Françoise
authors.initials: F
authors.lastname: Artières
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lina
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanchet
authors.forename: Michel
authors.initials: M
authors.lastname: Mondain
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA