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Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation |
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| Authors: | Alessandro Terrinoni Andrea Codispoti Valeria Serra Ernesto Bruno Michela Giustizieri Elena Campione |
| Affiliation: | a Biochemistry Laboratory, IDI-IRCCS, C/O Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy b I Dermatological Division, IDI-IRCCS, via dei Monti di Creta, 104, Rome 00167, Italy c ENT Department, University of Rome “Tor Vergata”, 00133 Rome, Italy d Department of Pharmacobiology, University of Calabria, via P. Bucci, Ed. Polifunzionale, 87036 Rende (CS), Italy e Laboratory of Experimental Neurology, Fondazione Santa Lucia IRCCS, Rome, Italy f Department of Diagnostic Imaging, University of Rome “Tor Vergata”, Italy g Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK |
| Abstract: | The autosomic dominant KID Syndrome (MIM 148210), due to mutations in GJB2 (connexin 26, Cx26), is an ectodermal dysplasia with erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. The Cx26 protein is a component of gap junction channels in epithelia, including the cochlea, which coordinates the exchange of molecules and ions. Here, we demonstrate that different Cx26 mutants (Cx26D50N and Cx26G11E) cause cell death in vitro by the alteration of intra-cellular calcium concentrations. These results help to explain the pathogenesis of both the hearing and skin phenotypes, since calcium is also a potent regulator of the epidermal differentiation process. |
| Keywords: | Connexin Gap junctions Mutations KID Syndrome Deafness Cell death |
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