Mutations in the gene of the gap junction protein Connexin 31 (CX31; other connexin 1 Laboratory of Molecular genes abbreviated by CX+#, i.e. Connexin 30 = CX30) have been demonstrated to be Otology, Epstein Laboratories, responsible for both autosomal dominant and recessive nonsyndromic hereditary hearing Department of Otolaryngologyimpairment (NHHI). In this study, we assessed the prevalence of CX31 mutations in pa-Head and Neck Surgery, tients who had undergone cochlear implant surgery for profound sensorineural hearing University of California, loss and investigate the potential relationship between sequence alterations in CX31 and San Francisco, CA, USA rehabilitative outcome. The single coding exon of CX31 was amplified by PCR from ge-2 Department of Otolaryngologynomic DNA of cochlear implant patients. Of the 57 patients, 14 patients (25%) had altered Head & Neck Surgery, sequence in CX31; sequence analysis identified 15 single base changes in the 14 for a Johns Hopkins University 13% (15/114) incidence of variant allele frequency in the study population. Four distinct Medical Center, single nucleotide transitions were recognized including: one previously undocumented sin-Baltimore, MA, USA
gle nucleotide transition (250G Η A) that resulted in an amino acid substitution at codon 84 (V84I) and three previously described single nucleotide polymorphisms (SNPs) (94C Η T, 357C Η T, and 798C Η T). A single patient exhibited the 357C Η T SNP in a homozygous state while the remaining patients' sequence variations were heterozygous. The novel V84I amino acid substitution occurred in the conserved second transmembrane domain of CX31 known to be critical for the regulation of voltage gating. However, the biologic consequence of this mutation and how it may relate to hearing loss is unknown. Rehabilitative outcome with cochlear implantation was similar in patients with and without CX31 mutations. Our data suggests that sequence alteration in CX31 is common in patients undergoing cochlear implantation and their rehabilitative outcome is unaffected.