Birkenhäger R, Zimmer A J, Maier W, Schipper J
Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde und Poliklinik, Forschungsgruppe Genetische Erkrankungen des Kopf- Hals-Bereiches, Universitätsklinikum Freiburg.
Laryngorhinootologie. 2006 Mar;85(3):191-6. doi: 10.1055/s-2005-870302.
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.
迄今为止，已鉴定出超过一百个非综合征性或综合征性耳聋的基因和基因座。连接蛋白26基因（GJB2）中的突变占常染色体隐性听力损失病例的50%。基因GJB2（连接蛋白26）、GJB3（连接蛋白31）和GJB6（连接蛋白31）位于13号染色体q11 - 12区域。在内耳中表达多达四种不同的连接蛋白。连接蛋白属于一组间隙连接蛋白。这些蛋白质可以寡聚化形成称为连接子的单膜通道。每个连接子由六个亚基组成，通过为离子、代谢物和第二信使的扩散提供通道，实现相邻细胞之间的通讯。
通过直接测序分析了连接蛋白26、30和31基因（GJB2、GJB3和GJB6）的每个外显子和侧翼剪接区域。
在所涉及的家族中，在连接蛋白26（GJB2）和连接蛋白30（GJB6）基因中检测到三个杂合突变。如果其中两个突变组合出现，即35DeltaG与146/147DeltaC以及35DeltaG与GJB6 - D13S1830，会导致听力损失和耳聋。
鉴于听力损失家族背景的证据，除了进行特定的听力诊断外，分析连接蛋白基因（GJB2、GJB3和GJB6）是否存在突变是合理的，以便通过早期使用助听器或植入人工耳蜗来促进语言发展。
