Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1splice site mutation affecting procollagen VII processing

Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermol ysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blister ing diseases characterized by scarring, loss of dermal-epidermal adhesion a nd altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant FEB family a glycine substitution m utation has been identified. We report a 33-year-old man affected by FEB sh owing abnormal AF and reduced immunostaining for type VII collagen. Mutatio n search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intro n boundary (33563del14), which resulted in the in-frame skipping of exon 11 5 with elimination of 29 amino acids from the pro-alpha 1(VII) polypeptide chain, Asa consequence, procollagen VII failed to be processed to mature co llagen Vn and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody, The prob and's father was a clinically unaffected heterozygous carrier of mutation 3 3563del14, whereas the maternal pathogenetic mutation has still not been id entified, This represents the first report of a recessive deletion mutation in FEB and extends the range of EBD phenotypes associated with mutation 33 563del14.