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.
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Acknowledgements
We greatly appreciate the cooperation of the families. We thank Corinne Chauve, Catherine Magnier and Sébastien Chardenoux for excellent technical assistance. This work was supported by the Fondation pour la Recherche Médicale, The Association Française contre les Myopathies, The Institut National de la Santé et de la Recherche Médicale, and The Association pour l'Etude de la Pathologie Pédiatrique.
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Feldmann, D., Denoyelle, F., Loundon, N. et al. Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene. Eur J Hum Genet 12, 279–284 (2004). https://doi.org/10.1038/sj.ejhg.5201147
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DOI: https://doi.org/10.1038/sj.ejhg.5201147
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