title: Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene.
abstract: Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France.
authors.affiliation: Service de Biochimie et de Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, AP-HP, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Feldmann
authors.forename: Françoise
authors.initials: F
authors.lastname: Denoyelle
authors.forename: Natalie
authors.initials: N
authors.lastname: Loundon
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Erea-Noel
authors.initials: EN
authors.lastname: Garabedian
authors.forename: Remy
authors.initials: R
authors.lastname: Couderc
authors.forename: Alain
authors.initials: A
authors.lastname: Joannard
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schmerber
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Jacques
authors.initials: J
authors.lastname: Leman
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.forename: Hélène
authors.initials: H
authors.lastname: Catros
authors.forename: Claude
authors.initials: C
authors.lastname: Ferrec
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Obstoy
authors.forename: Lucien
authors.initials: L
authors.lastname: Moati
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marlin
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26