Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene.
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.
Feldmann
Delphine
D
Service de Biochimie et de Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, AP-HP, Paris, France.
Denoyelle
Françoise
F
Loundon
Natalie
N
Weil
Dominique
D
Garabedian
Erea-Noel
EN
Couderc
Remy
R
Joannard
Alain
A
Schmerber
Sébastien
S
Delobel
Bruno
B
Leman
Jacques
J
Journel
Hubert
H
Catros
Hélène
H
Ferrec
Claude
C
Drouin-Garraud
Valérie
V
Obstoy
Marie-Françoise
MF
Moati
Lucien
L
Petit
Christine
C
Marlin
Sandrine
S
D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26