Clinical and genetic heterogeneity of erythrokeratoderma variabilis.
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.
Common
John E A
JE
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.
O'Toole
Edel A
EA
Leigh
Irene M
IM
Thomas
Anna
A
Griffiths
William A D
WA
Venning
Vanessa
V
Grabczynska
Sophie
S
Peris
Zdravko
Z
Kansky
Aleksej
A
Kelsell
David P
DP
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
D017630:Connexins; D012176:Retinoids; C068044:GJB3 protein, human; C076275:connexin 30.3