title: COL7A1 Recessive mutations in two siblings with distinct subtypes of dystrophic epidermolysis bullosa: pruriginosa versus nails only.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Sassari, Sassari, Italy. sarapru@hotmail.it
authors.forename: Sara
authors.initials: S
authors.lastname: Pruneddu
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Floriddia
authors.forename: Francesca
authors.initials: F
authors.lastname: Cottoni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
mesh_terms: D000368:Aged; D000483:Alleles; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007868:Leg Dermatoses / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D009260:Nail Diseases / Q000473:pathology*; D010375:Pedigree; D011537:Pruritus; D035781:Siblings; D014034:Toes / Q000473:pathology