Background: Dystrophic epidermolysis bullosa (DEB) is an inherited skin fragility disorder where blistering occurs in the sub-lamina densa zone at the level of anchoring fibrils (AFs) of the dermo-epidermal junction. Both autosomal dominant (DDEB) and recessive (RDEB) result from mutations in the type VII collagen gene (COL7A1).
Objective: The purpose of this study was to understand the genotype-phenotype correlation in Australian patients with DEB.
Methods: Skin biopsies from patients were processed for immunofluorescence mapping, the COL7A1 gene was screened for sequence variants.
Results: We report 14 Australian families with different forms of dystrophic epidermolysis bullosa (DEB) with 23 different COL7A1 allelic variants, nine of which were novel. Four cases of RDEB-HS combined two premature termination codon (PTC) variants and three other cases of RDEB-HS with combined PTC and spice-site or glycine substitution variants. G2043R, a de novo dominant variant, was also identified in this study. Four "silent" glycine substitutions were found in this study, G2775S, G1673R, G1338V and G2719A. EB17, with combined R2791W and G2210V variants, had a DDEB-Pasini phenotype, in contrast to two family members who had severe DDEB pruriginosa, with the same genotype.
Conclusion: In this study, the RDEB variants included nonsense variants, splice site variants, internal deletions or insertions, "silent" glycine substitutions within the triple helix or N or C terminal ends of the triple helix and non-glycine missense variants within the triple helix domain. DDEB usually involves glycine substitutions within the triple helix of COL7A1 although other missense variants or splice-site alterations may underlie some cases.