Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB)

RDEB is a rare bullous genodermatosis caused by mutations in COL7A1. Clinical features range from severe wounds to esophageal strictures and anemia. Prior work has identified associations of biallelic COL7A1 premature termination codon (PTC) mutations with more severe disease, likely from absent or severely truncated type VII collagen (C7), but genotype-phenotype associations for other mutations including splice site (SP) or missense (MS) mutations remain unexplored. We analyzed data from 83 RDEB patients for clinical characteristics and functional genotypes as defined by a mutation’s impact on C7 function using available literature and in silico predictions, classifying genotypes by degree of deleterious effect on C7 function as “severe” (PTC/PTC, n=40; PTC/SP, n=12), “moderate” (PTC/MS, n=20; SP/SP, n=2) and “mild” (SP/MS, n=4; MS/MS, n=5).