Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene

Prelingual non-syndromic (isolated) deafness is the most frequenthereditary sensory defect. In >80% of the cases, the mode oftransmission is autosomal recessive. To date, 14 loci have been identifiedfor the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, thegenes responsible have been characterized; they encode connexin 26 andmyosin VIIA, respectively. In order to evaluate the extent to which theconnexin 26 gene (Cx26) contributes to prelingual deafness, we searched formutations in this gene in 65 affected Caucasian families originating fromvarious countries, mainly tunisia, France, New Zealand and the UK. Six ofthese families are consanguineous, and deafness was shown to be linked tothe DFNB1 locus, 10 are small non consanguineous families in which thesegregation of the trait has been found to be compatible with theinvolvement of DFNB1, and in the remaining 49 families no linkage analysishas been performed. A total of 62 mutant alleles in 39 families wereidentified. Therefore, mutations in Cx26 represent a major cause ofrecessively inherited prelingual deafness since according to the presentresults they would underlie approximately half of the cases. In addition,one specific mutation, 30delG, accounts for the majority (approximately70%) of the Cx26 mutant alleles. It is therefore one of the most frequentdisease mutations so far identified. Several lines of evidence indicatethat the high prevalence of the 30delG mutation arises from a mutation hotspot rather than from a founder effect. Genetic counseling for prelingualdeafness has been so far considerably impaired by the difficulty indistinguishing genetic and non genetic deafness in families presenting witha single deaf child. Based on the results presented here, the developmentof a simple molecular test could be designed which should be ofconsiderable help.