Novel mutation in GJB4 gene (connexin 30.3) in a family with erythrokeratodermia variabilis.

© 2012 The Authors. doi: 10.2340/00015555-1436 Journal Compilation © 2012 Acta Dermato-Venereologica. ISSN 0001-5555 Erythrokeratodermia variabilis (EKV, MIM: 133200) is a rare autosomal dominant disorder characterized by the association of: (i) localized or generalized hyperkeratosis, and (ii) transient erythematous areas (1). Hyperkeratotic areas show well-demarcated, geographically outlined, and fixed plaques, in a strikingly symmetrical distribution. The hallmark of EKV is the continual occurrence of transient, sharply outlined, figured red patches of variable intensity that fade within a few hours or days. A very closely related phenotype, characterized by fixed and growing erythematous hyper­ keratosis symmetrical plaques, known as progressive symmetrical erythrokeratoderma of Gottron (PSEK, MIM: 133200), was initially seen as a distinct entity (2). The GJB3 gene, encoding connexin 31, is the major disease-causing gene of EKV (3). Mutations in a second gene, GJB4, encoding connexin 30.3, have been reported in both EKV and PSEK (4, 5), illustrating the genetic heterogeneity of these disorders. Thus, van Steensel (6) suggested that PSEK and EKV may be manifestations of the same genetic defect, and proposed the designation “erythrokeratodermia variabilis and progressiva” (EKV-P, MIM: 133200) to indicate the protean nature of the disorder. We describe here a large Algerian family, in which 9 affected patients presented with EKV-P phenotypes associated with a novel mutation (c.256T>A) in the GJB4 gene.