title: Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing.
abstract: Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant PEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by PEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-alpha1(VII) polypeptide chain. As a consequence, procollagen VII failed to be processed to mature collagen VII and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody. The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified. This represents the first report of a recessive deletion mutation in PEB and extends the range of EBD phenotypes associated with mutation 33563del14.
authors.affiliation: Department of Experimental Pathology, Università degli Studi di Bologna, Bologna, Italy. bettsch@kaiser.alma.unibo.it
authors.forename: C M
authors.initials: CM
authors.lastname: Betts
authors.forename: P
authors.initials: P
authors.lastname: Posteraro
authors.forename: A M
authors.initials: AM
authors.lastname: Costa
authors.forename: C
authors.initials: C
authors.lastname: Varotti
authors.forename: M
authors.initials: M
authors.lastname: Schubert
authors.forename: L
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: D
authors.initials: D
authors.lastname: Castiglia
mesh_terms: D000328:Adult; D003094:Collagen / Q000235:genetics*; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011347:Procollagen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000648:ultrastructure
chemical_list: D011347:Procollagen; D003094:Collagen