Mutations of the Connexin 26 gene in families with non-syndromic hearing loss

Abstract

Autosomal recessive non-syndromic hearing impairment (ARNSHI) is caused by mutations in the gap junction gene GJB2 (Connexin 26; Cx26) in numerous human populations. The aim of this study was to determine the frequency of six GJB2 mutations in 50 Syrian families with congenital deafness and in 180 controls. PCR-RFLP was used to detect the 35delG, 167delT, M34T, W24X, W77R and E47X mutations, and direct sequencing was performed for the 35delG mutation. The data revealed a high prevalence of the 35delG mutation among deaf families. Homozygous 35delG was detected in fifteen of the Syrian families (30%). A compound heterozygous genotype was observed in two families: one with the 35delG/167delT mutation (2%) and one with the 35delG/M34T mutation (2%). Nine families were heterozygous with no second identified mutation in Cx26: four with 35delG+/unknown (8%), four with 167delT/unknown (8%) and one with M34T/unknown (2%). The W24X, W77R and E47X mutations were not detected in any of the study subjects. Three individuals with the heterozygous 35delG genotype (1.66%) and five with the heterozygous 167delT genotype (2.77%) were detected among the controls. No other mutations were found among the controls. These results have important implications for the diagnosis and counseling of families with Cx26 deafness.