[Pseudodominants of two recessive connexin mutations in non-syndromic sensorineural hearing loss?]

Hitherto more than hundred genes and gene loci for non-syndromic or syndromic deafness have been identified. Mutations in the connexin 26 gene (GJB2) account for up to 50 % of the cases of autosomal recessive hearing loss. The genes GJB2 (Connexin 26), GJB3 (connexin 31) and GJB6 (connexin 31) are located on chromosome 13q11-12. In the inner ear up to four different connexins are expressed. Connexins appertain to a group of gap junction proteins. These proteins can oligomerize to form single-membrane channels called connexons. Each connexon is composed of six subunits, that allow communication between adjacent cells by providing a channel for diffusion of ions, metabolites and second messengers.

Each of the exons and flanking splice regions of the connexin 26, 30, and 31 genes (GJB2, GJB3, and GJB6) have been analysed by direct sequencing.

In the involved families three heterozygous mutations could be detected in the connexin 26 (GJB2) and connexin 30 (GJB6) genes. If a combination of two of those mutations occurs, 35DeltaG with 146/147DeltaC and 35DeltaG with GJB6-D13S1830 it results in hearing loss and deafness.

By evidences of a familial background of hearing loss it is reasonable to analyse the connexin genes (GJB2, GJB3 and GJB6) for mutations, additionally to a specific hearing diagnostic, in order to enhance linguistic development through hearing aid or CI-implantation at an early stage.