Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Ram Shankar Mani, Aparna Ganapathy, Rajeev Jalvi, C. R. Srikumari Srisailapathy, Vikas Malhotra, Shelly Chadha, Arun Agarwal, Arabandi Ramesh, Raghunath Rao Rangasayee, Anuranjan Anand

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (-23G>T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1+1G>A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

Original languageEnglish (US)
Pages (from-to)502-509
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number4
StatePublished - 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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