Cx26 deafness: mutation analysis and clinical variability

Mutations in the gap junction protein connexin 26 (Cx26) gene (GJB2) seem t o account for many cases of congenital sensorineural hearing impairment, th e reported prevalence being 33-50% in autosomal recessive cases and 10-37% in sporadic cases. The hearing impairment in these patients has been descri bed as severe or profound. We have studied 53 unrelated subjects with conge nital nonsyndromic sensorineural hearing impairment in order to evaluate th e prevalence and type of Cx26 mutations and establish better genotype-pheno type correlation. Mutations in the Cx26 gene were found in 53% of the subje cts tested, 35.3% of the autosomal recessive and 60% of the sporadic cases in our series. Three new mutations were identified. The hearing deficit var ied from mild to profound even in 35delG homozygotes within the same family . No evidence of progression of the impairment was found. Alterations of the Cx26 gene account for a large proportion of cases of con genital non-syndromic sensorineural deafness, so it seems appropriate to ex tend the molecular analysis even to subjects with mild or moderate prelingu al hearing impairment of unknown cause.