R Birkenhäger1, A J Zimmer, W Maier, J Schipper. 1. Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde und Poliklinik, Forschungsgruppe Genetische Erkrankungen des Kopf- Hals-Bereiches, Universitätsklinikum Freiburg. birkenhaeger@hno.ukl.uni-freiburg.de
Abstract
BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.