title: Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene.
abstract: Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.
authors.affiliation: Unité de Génétique de Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Denoyelle
authors.forename: D
authors.initials: D
authors.lastname: Weil
authors.forename: M A
authors.initials: MA
authors.lastname: Maw
authors.forename: S A
authors.initials: SA
authors.lastname: Wilcox
authors.forename: N J
authors.initials: NJ
authors.lastname: Lench
authors.forename: D R
authors.initials: DR
authors.lastname: Allen-Powell
authors.forename: A H
authors.initials: AH
authors.lastname: Osborn
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
authors.forename: A
authors.initials: A
authors.lastname: Middleton
authors.forename: M J
authors.initials: MJ
authors.lastname: Houseman
authors.forename: C
authors.initials: C
authors.lastname: Dodé
authors.forename: S
authors.initials: S
authors.lastname: Marlin
authors.forename: A
authors.initials: A
authors.lastname: Boulila-ElGaïed
authors.forename: M
authors.initials: M
authors.lastname: Grati
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
authors.forename: S
authors.initials: S
authors.lastname: BenArab
authors.forename: P
authors.initials: P
authors.lastname: Bitoun
authors.forename: G
authors.initials: G
authors.lastname: Lina-Granade
authors.forename: J
authors.initials: J
authors.lastname: Godet
authors.forename: M
authors.initials: M
authors.lastname: Mustapha
authors.forename: J
authors.initials: J
authors.lastname: Loiselet
authors.forename: E
authors.initials: E
authors.lastname: El-Zir
authors.forename: A
authors.initials: A
authors.lastname: Aubois
authors.forename: A
authors.initials: A
authors.lastname: Joannard
authors.forename: J
authors.initials: J
authors.lastname: Levilliers
authors.forename: E N
authors.initials: EN
authors.lastname: Garabédian
authors.forename: R F
authors.initials: RF
authors.lastname: Mueller
authors.forename: R J
authors.initials: RJ
authors.lastname: Gardner
authors.forename: C
authors.initials: C
authors.lastname: Petit
mesh_terms: D001315:Australia / Q000453:epidemiology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003241:Consanguinity; D003638:Deafness / Q000453:epidemiology / Q000235:genetics*; D005602:France / Q000453:epidemiology; D008040:Genetic Linkage; D006801:Humans; D007861:Lebanon / Q000453:epidemiology; D009520:New Zealand / Q000453:epidemiology; D015995:Prevalence; D017384:Sequence Deletion; D014416:Tunisia / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26