Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB-Pr) is a rare variant of DEB due to COL7A1 dominant and recessive mutations, which is characterized by severe itching and lichenoid or nodular prurigo-like lesions, mainly involving the extremities. Less than 30 patients have been described showing variable disease expression, and frequently, delayed age of onset. We report the clinical and molecular characterization of seven Italian DEB patients, three affected with recessive DEB-Pr and four with dominant DEB-Pr. In all the patients, the signs were typical of a mild DEB phenotype, until the onset of pruritus, which was followed by worsening of the clinical picture, with appearance of the distinctive lichenified lesions of DEB-Pr. Nine mutations were found in the COL7A1 gene, three of which were novel and one was de novo. DEB-Pr patients with either dominant or recessive mutations were shown to synthesize a normal or variably reduced amount of type VII collagen, which was correctly deposited at the dermal-epidermal junction. Since six of these mutations have been reported in DEB patients in the absence of intense pruritus, these data implicate a role of yet unidentified phenotype-modifying factors in the pathogenesis of DEB-Pr.

Our delineation of a laminin-5 mutational spectrum in the general Italian population provides a solid basis for expedited diagnosis, accurate genetic counselling and DNA-based prenatal testing for Italian families at risk for recurrence of HJEB.

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Dystrophic epidermolysis bullosa (DEB) is a rare, clinically heterogeneous, blistering genodermatosis inherited as either autosomal dominant or recessive trait. All DEB forms are caused by mutations in the COL7A1 gene, which encodes for type VII collagen, the major component of the anchoring fibrils ensuring epithelial-mesenchymal adhesion. Major determinants of clinical heterogeneity in DEB are COL7A1 mutation types and their consequences at mRNA and protein levels; nevertheless, siblings with the same genetic alterations can manifest highly variable clinical signs. Here, we report novel compound heterozygous recessive COL7A1 missense mutations in 2 siblings presenting different DEB clinical subtypes. Our findings document the rare occurrence of recessive inheritance for the nails only DEB variant and emphasize the role of acquired phenotype-modifying factors in DEB pruriginosa pathogenesis.

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