Novel and de novo glycine substitution mutations in the type VII collagen gene (COL7A1) in dystrophic epidermolysis bullosa: Implications for geneticcounseling

The dystrophic forms of epidermolysis bullosa (DEB) are due to mutations in the type VII collagen gene (COL7A1). In dominant DEB, a characteristic gen etic lesion is a glycine substitution mutation within the collagenous domai n of the protein. In this study, we have examined the molecular basis of si x new families in which the proband has clinical features and/or ultrastruc tural findings consistent with DEB. The results revealed a glycine substitu tion mutation in all six families, four of which are novel and previously u npublished. In three families with clinically unaffected parents, de novo m utations G2043R and G2040V were found. These results emphasize the predomin ance of glycine substitution mutations in dominant DEB, and indicate that i n some cases the phenotype is due to de novo dominant mutations.