title: Functional analysis of human Cx26 mutations associated with deafness.
abstract: Mutations in the connexin26 (Cx26) gene are not only a major cause of nonsyndromic deafness, but can also cause syndromic forms of hearing loss that are associated with palmoplantar keratoderma (PPK, i.e., Vohwinkel's syndrome). It is not clear how two very distinct pathologies can arise from different mutations within the same connexin gene. This review summarizes the available data on wildtype and mutant Cx26 channel behavior that has been obtained in the paired Xenopus oocyte assay. These results suggest that dominant and recessive loss of function mutations in Cx26 can cause nonsyndromic deafness, but cannot easily explain the syndromic forms exhibiting PPK. Dominant Cx26 mutations that can cause both PPK and deafness must show some additional alteration of function beyond a simple inhibition of Cx26 activity.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. twhite@hms.harvard.edu
authors.forename: T W
authors.initials: TW
authors.lastname: White
mesh_terms: D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology*; D016368:Frameshift Mutation; D017629:Gap Junctions / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D009865:Oocytes / Q000502:physiology; D014981:Xenopus
chemical_list: D017630:Connexins; C000607045:GJB2 protein, Xenopus; C000607042:GJB2 protein, human; D000072259:Connexin 26