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Giornale Italiano di Dermatologia e Venereologia 2005 June;140(3):263-70


language: English

Erythrokeratodermia variabilis: an update on clinics and genetics

Richard G.

Department of Dermatology and Cutaneous Biology Jefferson Medical College and Jefferson Institute of Molecular Medicine Thomas Jefferson University, Philadelphia, PA


Erythrokeratodermia variabilis (EKV) is a heritable disorder of cornification associated with non-inflammatory erythema. The majority of EKV patients harbor autosomal dominant missense mutations in the connexin genes for Cx31 or Cx30.3, which are expressed in the upper differentiated layers of the epidermis. Mutations exert a dominant negative effect and can interfere with protein folding and intracellular trafficking as well as with gap junction function, thus hindering gap junction communication and epidermal differentiation. Certain Cx31 mutations have been shown to induce cell death when expressed in vitro, yet the biological relevance of this finding remains to be established. The clinical presentations of Cx31 and Cx30.3 defects are strikingly similar, although circinate or gyrate erythema appear to be a specific feature of Cx30.3 mutations. In addition, there is new molecular evidence for the existence of an autosomal recessive variant of EKV due to homozygous mutations in Cx31, which has important implications for determining the recurrence risk for EKV in families with a sporadic case. Finally, connexin gene mutations account for EKV in most but not all individuals, underscoring that other gene(s) might be involved in the pathogenesis of EKV. Hence, a complex understanding of the different clinical forms of erythrokeratodermas and their etiology beckons further thorough clinical and molecular analyses in large cohorts of patients.

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