Article Text

Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment
  1. DAVID O ROBINSON

    Statistics from Altmetric.com

    Over 40 loci for deafness have been genetically mapped but only in very recent years have causative genes been identified. Two of these are connexins and this promted Xiaet al to search for new human connexin genes and look for mutations in families with deafness. From a database, two overlapping ESTs were identified with 83% identity to rat Gjb3 and a homologous fragment amplified from human DNA. This identified human GJB3 (connexin 31) which mapped to 1p32-p35. RT-PCR analysis showed it to be expressed in the inner ear. Of six families with sensorineural deafness linked to 1p32-p35, two were found to have mutations in the connexin 31 gene. One resulted in an amino acid change and the other in a premature stop codon causing absence of part of the C terminus of the protein. Both of these mutations were in regions highly conserved in other connexins. In both families, inheritance was autosomal dominant but males were affected with progressive bilateral high frequency hearing impairment with onset from 20 to 40 years of age, whereas females were either unaffected or much less severely affected. A significant proportion of families with AD hearing loss show linkage to 1p32-35, so Xia et al may have identified a common cause of deafness. Interestingly, in the same issue ofNature Genetics, an independent group describe the identification of the same gene but found mutations in a different region to be responsible for erythrokeratodermia variabilis in which deafness is not a feature. These findings are discussed in the “News and views” section and represent an interesting example of different mutations in the same gene being responsible for two completely different phenotypes.

    View Abstract

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.