title: Clinical and genetic heterogeneity of erythrokeratoderma variabilis.
abstract: The skin disease erythrokeratoderma variabilis (EKV) has been shown to be associated with mutations in GJB3 and GJB4 encoding connexin (Cx)31 and Cx30.3, respectively. Gap junctions composed of Cx proteins are intracellular channels providing a mechanism of synchronized cellular response facilitating metabolic and electronic functions of the cell. In the skin, Cx31 and Cx30.3 are expressed in the stratum granulosum of the epidermis with a suggested role in late keratinocyte differentiation. Molecular investigations of GJB3 and GJB4 were performed in five pedigrees and three sporadic cases of EKV. Mutational analyzes revealed disease-associated Cx31 or Cx30.3 mutations in only three probands of which two were novel mutations and one was a recurrent mutation. These genetic studies further demonstrate the heterogeneous nature of the erythrokeratodermas as not all individuals that were clinically diagnosed with EKV harbor Cx31 or Cx30.3 mutations.
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London, UK.
authors.forename: John E A
authors.initials: JE
authors.lastname: Common
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Anna
authors.initials: A
authors.lastname: Thomas
authors.forename: William A D
authors.initials: WA
authors.lastname: Griffiths
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venning
authors.forename: Sophie
authors.initials: S
authors.lastname: Grabczynska
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Peris
authors.forename: Aleksej
authors.initials: A
authors.lastname: Kansky
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012176:Retinoids / Q000627:therapeutic use
chemical_list: D017630:Connexins; D012176:Retinoids; C068044:GJB3 protein, human; C076275:connexin 30.3