Features of epidermolysis bullosa simplex due to mutations in the ectodomain of type XVII collagen

Summary Background  Mutations in COL17A1 , coding for type XVII collagen, cause junctional epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. Objectives  To identify the COL17A1 mutations in a child with reduced type XVII collagen expression and intraepidermal blister formation. Patient and methods  Protein expression and level of tissue separation were studied by immunofluorescence and electron microscopy. The mutations were identified by analysing the patient's DNA and mRNA. Results  Immunofluorescence microscopy performed on nonlesional skin demonstrated absence of the type XVII collagen endodomain and presence, although reduced, of the shed ectodomain. Electron microscopy showed that the plane of cleavage was through the basal cells, not through the lamina lucida. Two heterozygous mutations were identified in COL17A1 : a new 3′‐acceptor splice‐site mutation in intron 21 (1877–2A→C), and a deletion in exon 48 (3432delT). The splice‐site mutation in intron 21 results in alternative transcripts of which two are in‐frame, with deletions of the first nine codons of exon 22 and the entire exon 22, respectively. By Western blot analysis, a type XVII collagen molecule was detected that was slightly smaller than normal. Conclusions  Occasionally mutations in the COL17A1 gene may result in split levels suggesting epidermolysis bullosa simplex rather than junctional epidermolysis bullosa.