PRELINGUAL DEAFNESS - HIGH PREVALENCE OF A 30DELG MUTATION IN THE CONNEXIN 26 GENE

Prelingual non-syndromic (isolated) deafness is the most frequent here ditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the gen es responsible have been characterized; they encode connexin 26 and my osin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searche d for mutations in this gene in 65 affected Caucasian families origina ting from various countries, mainly Tunisia, France, New Zealand and t he UK. Six of these families are consanguineous, and deafness was show n to be linked to the DFNB1 locus, 10 are small non consanguineous fam ilies in which the segregation of the trait has been found to be compa tible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles i n 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since accor ding to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for th e majority (similar to 70%) of the Cx26 mutant alleles. It is therefor e one of the most frequent disease mutations so far identified. Severa l lines of evidence indicate that the high prevalence of the 30delG mu tation arises from a mutation hot spot rather than from a founder effe ct. Genetic counselling for prelingual deafness has been so far consid erably impaired by the difficulty in distinguishing genetic and non ge netic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular t est could be designed which should be of considerable help.