Mutations in the gene encoding gap junction protein β-3 associated with autosomal dominant hearing impairment

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Abstract
Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate1. More than 50% of the cases of profound early-onset deafness are caused by genetic factors2,3. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss4. Mutations in the gene encoding connexin 26 (GJB2) cause both autosomal recessive and dominant forms of hearing impairment5,6. To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene (GJB3) encoding human gap junction protein β-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.