Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa

The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. The ultrastructural hallmark of DEB is abnormalities in the anchoring fibrils. A recessively inherited variant, the mitis type of DEB (M-RDEB), is characterized by a mild phenotype, including the absence of mutilating scarring of the hands and feet. In this study, we demonstrate that M-RDEB results from the combination of a premature termination codon mutation in one COL7A1 allele, while the other mutation consists of different types of genetic lesions. These results define M-RDEB as a distinct clinical entity at the molecular level.