Author:
Lee Jack R.,White Thomas W.
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 inGJB2, 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 35ΔG, a frameshift mutation leading to an early stop codon. The large number of deaf individuals homozygous for 35ΔG 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.
Publisher
Cambridge University Press (CUP)
Subject
Molecular Biology,Molecular Medicine
Reference155 articles.
1. http://webh01.ua.ac.be/hhh/ A listing of studied mouse models for varying forms of deafness and hearing impairment can be found at the deafness mouse mutants website:
2. http://www.hgmd.cf.ac.uk/ac/index.php The deafness website is a collection of known genes and their loci present in hereditary hearing loss:
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4. Transport and Function of Cx26 Mutants Involved in Skin and Deafness Disorders
5. A Novel GJB2 (Connexin 26) Mutation, F142L, in a Patient with Unusual Mucocutaneous Findings and Deafness
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