454 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) with more disease, likely absent or severely truncated type VII collagen (C7), but genotype-phenotype for other including splice site (SP) missense (MS) remain unexplored. We analyzed data 83 patients clinical characteristics functional genotypes as defined mutation’s impact on C7 function using available literature silico predictions, classifying degree deleterious effect “severe” (PTC/PTC, n=40; PTC/SP, n=12), “moderate” (PTC/MS, n=20; SP/SP, n=2) “mild” (SP/MS, n=4; MS/MS, n=5). Mean age was 24 years. Genotype severity follows: 63% severe, 27% moderate 11% mild. 89% subjects mild had 2 the collagenous domain (vs 46% genotypes, p=0.05). Greater mutation correlated disease burden higher frequency generalized blistering limited; severe=90% vs moderate=73% mild=56%, p<0.01), complete hand pseudosyndactyly (37% 25% 22%, p=0.02) loss fingernails (79% 59% 33%, p<0.01). Mutation also presence extracutaneous findings anemia 55% 44%, ocular p<0.01) use gastrostomy tube (48% 23% p=0.02). Our suggest that like PTC/PTC mutations, PTC/SP correlate phenotypes, while SP/MS MS/MS less disease. Further study larger samples needed improve genotype-related prognostics patients.