Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment

Mutations in the connexin 31 (GJB3) gene have been found in subjects with d ominant and recessive deafness and in patients with erythrokeratodermia var iabilis, We report here a dominant mutation in the GJB3 gene (D66del) in a family affected with peripheral neuropathy and sensorineural hearing impair ment, A wide range of disease severity for peripheral neuropathy, from asym ptomatic cases to subjects with chronic skin ulcers in their feet and osteo myelitis leading to amputations, was detected in D66del patients. Mild, oft en asymmetrical, hearing impairment was found in all but one patient with m utation D66del of this family and the same mutation was present in an indep endent family ascertained because of hearing impairment. We have found mous e connexin 31 (Gjb3) gene expression in the cochlea and in the auditory and sciatic nerves, showing a pattern similar to that of Gjb1 (connexin 32), o f which the human ortholog (GJB1) is involved in X-linked peripheral neurop athy, This expression pattern, together with auditory-evoked brainstem anom alous response in D66del patients, indicates that hearing impairment due to GJB3 mutations involves alterations in both the cochlea and the auditory n erve. Peripheral neuropathy is the third phenotypic alteration linked to GJ B3 mutations, which enlarges the list of genes that cause this group of het erogeneous disorders.