John Libbey Eurotext

European Journal of Dermatology


Erythrokeratodermia variabilis: Report of two cases and a novel missense variant in GJB4 encoding connexin 30.3 Volume 22, issue 2, March-April 2012


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Department of Genetics, Institute of Child Health, “Aghia Sophia” Children's Hospital, Athens 11527, Greece, 1 st Department of Dermatology & Venereology, “Andreas Sygros” Hospital, Athens, Greece
  • Key words: Erythrokeratodermia variabilis, EKV, GJB3, GJB4, polymorphism, variant
  • DOI : 10.1684/ejd.2011.1617
  • Page(s) : 182-6
  • Published in: 2012

Erythrokeratodermia variabilis (EKV) is characterized by migrating red patches resembling a geographical map, and by localized or generalized hyperkeratosis with scaling of the skin. The onset is usually at birth or during infancy, and the disease persists throughout life. EKV is mainly inherited as an autosomal dominant disease, although recessive transmission has occasionally been reported. Mutations associated with EKV have been identified in the connexin (Cx) genes GJB3 (Cx31) and GJB4 (Cx30.3), however, several cases of EKV have been tested negative for mutations in these two Cx genes. Here, we report our findings of the clinical, histological, and molecular examinations performed in two unrelated sporadic cases of EKV. The molecular screening involved bidirectional sequencing of the coding regions of the GJB3 and GJB4 genes and revealed the existence of a novel c.295G>A missense variant in the GJB4 gene found in homozygosity in one case. The substitution was found to result in a p.E99K change of the Cx30.3 protein, an alteration predicted to have a benign rather than a damaging effect on the protein function.