title: From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome.
abstract: The keratitis-ichthyosis-deafness (KID) syndrome is characterized by corneal, skin, and hearing abnormalities. KID has been linked to heterozygous dominant missense mutations in the GJB2 and GJB6 genes, encoding connexin26 and 30, respectively. In vitro evidence indicates that KID mutations lead to hyperactive (open) hemichannels, which in some cases is accompanied by abnormal function of gap junction channels. Transgenic mouse models expressing connexin26 KID mutations reproduce human phenotypes and present impaired epidermal calcium homeostasis and abnormal lipid composition of the stratum corneum affecting the water barrier. Here we have compiled relevant data regarding the KID syndrome and propose a mechanism for the epidermal aspects of the disease.
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: García
authors.affiliation: LIMES (Life and Medical Sciences) Institute, University of Bonn, Bonn, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Bosen
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Paula
authors.initials: P
authors.lastname: Mujica
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Amaury
authors.initials: A
authors.lastname: Pupo
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Flores-Muñoz
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Oscar
authors.initials: O
authors.lastname: Jara
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: González
authors.affiliation: LIMES (Life and Medical Sciences) Institute, University of Bonn, Bonn, Germany. Electronic address: k.willecke@uni-bonn.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile. Electronic address: agustin.martinez@uv.cl.
authors.forename: Agustín D
authors.initials: AD
authors.lastname: Martínez
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D002463:Cell Membrane Permeability / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004817:Epidermis / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007634:Keratitis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D014883:Water-Electrolyte Imbalance / Q000235:genetics / Q000503:physiopathology
chemical_list: D015220:Calcium Channels; D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26
keywords: Cx; GJCs; HCs; KID; PPK; connexin; gap junction channels; hemichannels; keratitis-ichthyosis-deafness; palmoplantar keratoderma