CONNEXIN-26 MUTATIONS IN SPORADIC AND INHERITED SENSORINEURAL DEAFNESS

Background Hearing impairment affects one infant in 1000 and 4% of peo ple aged younger than 45 years. Congenital deafness is inherited or ap parently sporadic. We have shown previously that DFNB1 on chromosome 1 3 is a major locus for recessive deafness in about 80% of Mediterranea n families and that the connexin-26 gene gap junction protein beta 2 ( GJB2) is mutated in DFNB1 families, We investigated mutations in the G JB2 gene in familial and sporadic cases of deafness. Methods We obtain ed DNA samples from 82 families from Italy and Spain with recessive no n-syndromic deafness and from 54 unrelated participants with apparentl y sporadic congenital deafness. We analysed the coding region of the G JB2 gene for mutations. We also tested 280 unrelated people from the g eneral populations of Italy and Spain for the frameshift mutation 35de lG. Findings 49% of participants with recessive deafness and 37% of sp oradic cases had mutations in the GJB2 gene; The 35delG mutation accou nted for 85% of GJB2 mutations, six other mutations accounted for 6% o f alleles, and no changes in the coding region of GJB2 were detected i n 9% of DFNB1 alleles., The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87). Interpretation Mutations in the GJB2 gene are a major cau se of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. Identif ication of 35delG and other mutations in the GJB2 gene should facilita te diagnosis and counselling for the most common genetic form of deafn ess.