Prelingual Deafness: High Prevalence of a 30delG Mutation in the Connexin 26 Gene

Prelingual non-syndromic (isolated) deafness is themost frequent hereditary sensory defect. In >80% of thecases, the mode of transmission is autosomal recessive.To date, 14 loci have been identified for the recessiveforms (DFNB loci). For two of them, DFNB1 and DFNB2,the genes responsible have been characterized; theyencode connexin 26 and myosin VIIA, respectively. Inorder to evaluate the extent to which the connexin 26gene (Cx26) contributes to prelingual deafness, wesearched for mutations in this gene in 65 affectedCaucasian families originating from various countries,mainly Tunisia, France, New Zealand and the UK. Six ofthese families are consanguineous, and deafness wasshown to be linked to the DFNB1 locus, 10 are small nonconsanguineous families in which the segregation of thetrait has been found to be compatible with theinvolvement of DFNB1, and in the remaining 49 familiesno linkage analysis has been performed. A total of 62mutant alleles in 39 families were identified. Therefore,mutations in Cx26 represent a major cause ofrecessively inherited prelingual deafness sinceaccording to the present results they would underlieapproximately half of the cases. In addition, one specificmutation, 30delG, accounts for the majority ( ∼70%) of theCx26 mutant alleles. It is therefore one of the mostfrequent disease mutations so far identified. Severallines of evidence indicate that the high prevalence of the30delG mutation arises from a mutation hot spot ratherthan from a founder effect. Genetic counselling forprelingual deafness has been so far considerablyimpaired by the difficulty in distinguishing genetic andnon genetic deafness in families presenting with a singledeaf child. Based on the results presented here, thedevelopment of a simple molecular test could bedesigned which should be of considerable help.INTRODUCTIONProfound or severe prelingual deafness affects one child in athousand in developed countries (1). It is a major impairment as