title: Connexin-26 mutations in deafness and skin disease.
abstract: Gap junctions allow the exchange of ions and small molecules between adjacent cells through intercellular channels formed by connexin proteins, which can also form functional hemichannels in nonjunctional membranes. Mutations in connexin genes cause a variety of human diseases. For example, mutations in GJB2, the gene encoding connexin-26 (Cx26), are not only a major cause of nonsyndromic deafness, but also cause syndromic deafness associated with skin disorders such as palmoplantar keratoderma, keratitis-ichthyosis deafness syndrome, Vohwinkel syndrome, hystrix-ichthyosis deafness syndrome and Bart-Pumphrey syndrome. The most common mutation in the Cx26 gene linked to nonsyndromic deafness is 35DeltaG, a frameshift mutation leading to an early stop codon. The large number of deaf individuals homozygous for 35DeltaG do not develop skin disease. Similarly, there is abundant experimental evidence to suggest that other Cx26 loss-of-function mutations cause deafness, but not skin disease. By contrast, Cx26 mutations that cause both skin diseases and deafness are all single amino acid changes. Since nonsyndromic deafness is predominantly a loss-of-function disorder, it follows that the syndromic mutants must show an alteration, or gain, of function to cause skin disease. Here, we summarise the functional consequences and clinical phenotypes resulting from Cx26 mutations that cause deafness and skin disease.
authors: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, New York 11794-8661, USA.
authors: Jack R
authors: JR
authors: Lee
authors: Thomas W
authors: TW
authors: White
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D017629:Gap Junctions; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology; D007645:Keratoderma, Palmoplantar / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012181:Retrocochlear Diseases / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics; D013577:Syndrome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26