RESUMEN
A large pedigree with erythrokeratodermia variabilis (EKV) and erythema gyratum repens-like lesions is described. Clinical, laboratory, and histologic findings of this family are presented. The differential diagnoses of the following dermatoses with an erythematous and a hyperkeratotic component are discussed: erythrokeratodermia variabilis (Mendes da Costa), progressive symmetric erythrokeratoderma (Gottron), loricrin keratoderma, erythrokeratoderma en cocardes (Degos), Netherton syndrome, keratitis-ichthyosis-deafness (KID) syndrome, erythrokeratolysis hiemalis (Oudtshoorn disease), and nonbullous congenital ichthyosiform erythroderma.
Asunto(s)
Predisposición Genética a la Enfermedad , Hiperqueratosis Epidermolítica/genética , Hiperqueratosis Epidermolítica/patología , Adulto , Anciano , Biopsia con Aguja , Niño , Eritema/genética , Eritema/patología , Femenino , Heterocigoto , Humanos , Eritrodermia Ictiosiforme Congénita/genética , Eritrodermia Ictiosiforme Congénita/patología , Inmunohistoquímica , Lactante , Recién Nacido , Israel , Masculino , Persona de Mediana Edad , Linaje , Pronóstico , Muestreo , Índice de Severidad de la Enfermedad , Enfermedades Cutáneas Genéticas/diagnósticoRESUMEN
Erythrokeratodermia variabilis (EKV) is a skin disorder characterized by variable (transient) erythemas and fixed keratosis. The disorder maps to chromosome 1p34-35, a location that contains the GJB3 gene encoding the gap junction protein connexin 31. Until now, only heterozygote mutations in the form of dominant inheritance have been described in this gene associated with EKV. We report here a homozygote mutation in the connexin 31 gene, found in a family that shows recessive inheritance of the disorder, thus providing the first molecular support for a recessive variant of EKV. The entire GJB3 coding sequence was scanned for mutations by sequencing. We detected a T-->C transition at position 101 of the coding sequence, which replaces a leucine with a proline at residue 34 of the protein (L34P). Evolutionary analysis shows that this mutation is located at a highly conserved region of connexin in the first putative transmembrane helix (TMH). In transfected keratinocytes, L34P connexin 31 had a cytoplasmic distribution, suggesting that the mutant form of this protein will not form normal gap junctions between adjacent cells. The change of leucine to proline is likely to alter the structure of the first TMH of connexin by inducing a kink, thus influencing connexon structure and function.