A NOVEL MUTATION IN THE HELIX TERMINATION PEPTIDE OF KERATIN-5 CAUSING EPIDERMOLYSIS-BULLOSA SIMPLEX DOWLING-MEARA

Epidermolysis bullosa simplex Dowling-Meara (MIM# 1317600) is the most severe of the three common epidermolysis bullosa simplex subtypes. In addition to the palmoplantar distribution seen in other epidermolysis bullosa simplex subtypes, extensive herpetiform blistering spontaneou sly develops on the trunk and limbs and may lead to scarring or milia formation, The keratin 5 and keratin 14 genes encode proteins that for m the primary structural components of the basal epidermal keratinocyt es, mutations in either of these genes can cause epidermolysis bullosa simplex, In this study we sequenced these genes in a family with epid ermolysis bullosa simplex Dowling-Meara. We report a novel T to C tran sition in the helix termination peptide of K5 that causes a nonconserv ative substitution of a highly conserved amino acid within this critic al region (I466T). This mutation adds to those previously reported and provides further evidence of phenotype-genotype correlation in epider molysis bullosa simplex.