Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with nonsyndromic hearing loss

Se Kyung Oh, Soo Young Choi, Song Hee Yu, Kyu Yup Lee, Jeong Hwa Hong, Sung Won Hur, Sang Jeong Kim, Chang Jin Jeon, Un Kyung Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


A number of genes responsible for hearing loss are related to ion recycling and homeostasis in the inner ear. Connexins (Cx26 encoded by GJB2, Cx31 encoded by GJB3 and Cx30 encoded by GJB6) are core components of gap junctions in the inner ear. Gap junctions are intercellular communication channels and important factors that are associated with hearing loss. To date, a molecular genetics study of GJB3 and GJB6 as a causative gene for hearing loss has not been performed in Korea. This study was therefore performed to elucidate the genetic characteristics of Korean patients with nonsyndromic sensorineural hearing loss and to determine the pathological mechanism of hearing loss by analyzing the intercellular communication function of Cx30 and Cx31 variants. Sequencing analysis of the GJB3 and GJB6 genes in our population revealed a total of nine variants, including four novel variants in the two genes. Three of the novel variants (Cx31-p.V27M, Cx31-p.V43M and Cx-30-p.I248V) and two previously reported variants (Cx31-p.V84I and Cx30-p.A40V) were selected for functional studies using a pathogenicity prediction program and assessed for whether the mutations were located in a conserved region of the protein. The results of biochemical and ionic coupling tests showed that both the Cx31-p.V27M and Cx31-p.V84I variants did not function normally when each was expressed as a heterozygote with the wild-type Cx31. This study demonstrated that two variants of Cx31 were pathogenic mutations with deleterious effect. This information will be valuable in understanding the pathogenic role of GJB3 and GJB6 mutations associated with hearing loss.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number1
StatePublished - Jan 2013


  • Connexin
  • Functional study
  • Gap junction
  • Hearing loss
  • Variant


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