GJB2 mutations: Genotypic and phenotypic correlation in a cohort of 690 hearing-impaired patients, toward a new...

To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with GJB2 mutations.

Case series.

Collaborative study in referral centers, institutional practice.

A total of 690 hearing-impaired patients were genotypically and phenotypically described. The mutations of GJB2 and GJB6 were studied. Heterozygous patients were searched for another mutation by microsatellite approach.

Prevalence of GJB2 mutations, microsatellite approach, hearing-impairment.

In 498 patients (72,17% of the cohort), no mutation was found. Homozygotous patients were 59 (8,55%), with 51 for c.35delG, 6 for p.M34T and 2 for GJB6. Compound heterozygous were 64 (9,28%) with 56 c.35delG-others mutations. Genotypes with biallelic non sense mutations had a high risk of severe to profound hearing impairment. It was frequently milder in compound heterozygotes than in c.35delG homozygotes. Heterozygous patients were 69 (10%) with 21 c.35delG, 20 p.M34T and 28 others mutations. We selected patients with a complete historical medical file (clinical and audiometric data). Then, we performed a microsatellite approach (multiplex PCR of short DNA fragments) to localize a new pathologic allele. Seventeen heterozygous patients were studied. Six patients (35%) showed the same haplotype. They were compound heterozygous bearing a new pathologic allele.

Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness. A new haplotype for GJB2 is described but the exact mutation remains unknown.