Connexin 31, deafness and erythrokeratodermia variabilis

Mutations in Connexin 31 (GJB3)have been detected in two different disorders, deafness (Xia et al. 1998, Liu et al.) and erythrokeratodermia variabilis (EKV) (Richard et al. 1998).

GJB3 in skin

As other connexins, GJB3 was a good candidate for skin disorders; it is expressed in hair follicles and skin, and specially in differentiating keratinocytes. As GJB3 localizes in the same chromosomal region as the locus for EKV Richard et al. (1998) screened the gene for mutations in different families with EKV, and identified three missense mutations.

Dominant deafness and GJB3

Xia et al. (1998) had cloned GJB3 and screened for mutations in patients suffering several hereditary disorders linked to 1p32-p36, such as deafness, Charcot-Maire-Tooth, erythrokeratodermia and ptosis.
They identified two mutations, one missense and one nonsense, in two late onset deafness families, while no mutations were detected in patients with other disorders. The penetrance of the GJB3 mutations in the deafness phenotype was variable. Four male adult patients presented progressive deafness, while in two female carriers of mutations in GJB3 hearing impairment was either subclinical or non detectable. GJB3 maps within the DFNA2 locus.

Recessive deafness and GJB3

Liu et al. (unpublished results) also identify in GJB3 two different mutations, both occurring in the same amino acid, Isoleucine 141. One of the mutations consists in the complete (in-frame) deletion of this amino acid, the other one is a missense mutation that changes this amino acid into valine.