Effects of GJB2 genotypes on the audiological phenotype: Variability is present for all genotypes

Summary Background and aim Recent studies have revealed a genotype–phenotype correlation for mutations in the GJB2 gene. Since ethnic difference may have an effect for the degree of hearing loss due to background genes, we aimed to search for confirmation of previously suggested genotype–phenotype correlation in GJB2 deafness in the Turkish population. Methods Pure tone audiograms of 63 unrelated probands with GJB2 -associated hearing loss having 15 different mutations were obtained and evaluated for correlation between the degree of hearing loss and genotypes. Results Three GJB2 genotypes identified in more than one family were homozygous c.35delG (44 probands), homozygous p.E120del (four probands) and c.[35delG] + [IVS1 + 1G > A] (two probands). No statistical difference for the degree of hearing loss was observed when the genotypes were compared individually or grouped according to their effects on the protein. The most likely explanation for this result is the relatively small size of the studied population. Degree of hearing loss was variable in c.35delG and p.E120del homozygotes. Intra-familial phenotypic variability was present for some genotypes. The detailed audiological data for homozygous p.E120del and c.[35delG] + [328delG] genotypes are reported for the first time in this study. Conclusion Previously reported genotype–phenotype correlations for the GJB2 deafness should be cautiously interpreted during the clinical counseling since variability in the degree of hearing loss is present for all GJB2 genotypes.