Identification of a new connexin gene GJA11 (Cx59) using degenerate PCR primers

Abstract

Introduction Connexins (Cx) comprise a family of homologous proteins that are involved in the intercellular exchange of ions and small metabolites between adjacent cells. So far, mutations in seven different connexins have been found in humans, each resulting in a genetic disease.

Methods Based on the sequence alignment of known human Cx genes, we developed degenerate PCR primers that we anticipated would amplify members of the Cx gene family, in order to identify novel Cx genes.

Results By subcloning and sequencing the PCR products, we identified a previously unidentified connexin gene that we named Cx59 (GJA11). Using FISH we localized the GJA11 gene to chromosome 1p34, and by the analysis of a YAC contig of this region, we mapped this gene within the linkage interval of an Indonesian family with autosomal dominant nonsyndromic hearing loss (ADNSHL). Because mutations in other connexins, namely GJB3 (Cx31) and GJB6 (Cx30), lead to similar forms of ADNSHL, GJA11 (Cx59) was a very strong candidate gene. Therefore, we performed mutation analysis of the coding region of GJA11 in patients of this Indonesian family, but no disease-causing mutation was found.