Dystrophic epidermolysis bullosa pruriginosa is not associated with frequent FLG gene mutations.
BACKGROUND
Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr; OMIM 604129) is a rare manifestation of dystrophic epidermolysis bullosa (DEB), characterized by pruritus, nodular prurigo-like lesions and fragility of the skin mainly in the extremities. Fewer than 40 patients with autosomal dominant or recessive inheritance, or sporadic DEB-Pr, have been described in the literature.


OBJECTIVE
To disclose mutations in DEB-Pr and to elucidate the role of other pathogenic factors which may influence the pruriginous phenotype.


METHODS
Seven patients with typical clinical features of DEB-Pr were studied.


RESULTS
In all patients, mutations in the gene encoding collagen VII (COL7A1) were disclosed, two of them novel (p.G2623V, p.E2736K). Three mutations were dominant, three recessive and one de novo. In the families with dominant DEB there were one or more members with DEB-Pr, but also at least one affected sibling who did not develop DEB-Pr. In six of seven patients, the clinical history revealed factors that initially induced pruritus, such as atopy, pregnancy, thyroid hormone imbalance, diabetes, infections and contact sensitization. Common filaggrin mutations were ruled out in all patients and normal filaggrin staining was found in the skin samples.


CONCLUSIONS
DEB-Pr develops as a result of COL7A1 gene mutations and acquired phenotype-modifying factors. Filaggrin mutations did not contribute to the pruriginous phenotype in the present patient cohort.
Department of Dermatology, University Medical Center Freiburg, 79104 Freiburg, Germany. hauke.schumann@uniklinik-freiburg.de
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Kohlhase
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Bruckner-Tuderman
D000293:Adolescent; D002648:Child; D024143:Collagen Type VII / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011536:Prurigo / Q000209:etiology / Q000235:genetics; D011537:Pruritus / Q000209:etiology / Q000235:genetics
D024143:Collagen Type VII; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins