Connexin 30 and hearing impairment

Despite GJB2 mutations are found in a high number of families with deafness, there are families linked to chromosome 13 that do not have mutations in GJB2 or only have mutations in one GJB2 allele. This suggests the presence of other genes involved in deafness located in the same chromosomal region.

Grifa et al. cloned the human Connexin 30 (GJB6) gene, localized it in the same YAC contig of GJB2 on 13q11 and have shown expression of GJB6 in the mouse cochlea. The analysis of deaf patients lead to the identification of a missense mutation in a family with dominant hearing impairment, although with phenotypic variation. The authors have demonstrated by studies in Xenopus Laevis that the GJB6 T5M mutation has a dominant negative effect.

Lerer et al (2001) identified a deletion encompassing exon 1 of GJB6 that is the cause of deafness in 7 patients from 4 families carrying another recessive mutation in the GJB2 gene in trans. A similar mutation has also been described by Pallares et al. (2002), who have detected it in French patients or patients with a Spanish origin, and by del Castillo et al. (2002), who have also identified it in several Spanish families. For more information, please see the " big deletions and insertions affecting connexin genes" link.