A RECURRENT GLYCINE SUBSTITUTION MUTATION, G2043R, IN THE TYPE-VII COLLAGEN GENE (COL7A1) IN DOMINANT DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the t ype VII collagen gene (COL7A1), Nearly all cases of dominant DEB are c aused by glycine substitution mutations occurring within the triple he lical region of type VII collagen, and most of the mutations are uniqu e to individual families. In this study, we identified a patient of Hi spanic-Mexican origin with a mild form of DEB, which resulted from a d e novo dominant glycine substitution, G2043R, in exon 73 of COL7A1. We also investigated a Scottish family with a three-generation pedigree of dominant DEB, in whom the same glycine to arginine substitution mut ation was demonstrated. This particular mutation has also been detecte d previously in three other families with dominant DEB: one Italian, o ne Hungarian and one Norwegian. Given the widespread geographical dist ribution of this mutation and the demonstration of its occurrence as a de novo event, G2043R therefore represents the first example of a mut ational hotspot in dominant DEB. Interestingly, although both the Mexi can and Scottish families we studied had some clinical features in kee ping with the Pasini form of the disorder, there was considerable inte rfamilial variability as well as intrafamilial diversity in the affect ed individuals.