A GLYCINE-TO-ARGININE SUBSTITUTION IN THE TRIPLE-HELICAL DOMAIN OF TYPE-VII COLLAGEN IN A FAMILY WITH DOMINANT DYSTROPHIC EPIDERMOLYSIS-BULLOSA

We recently demonstrated strong genetic linkage between the type VII c ollagen gene (COL7A1) and both the dominant and recessive forms of dys trophic epidermolysis bullosa. In this study, we searched for mutation s in dominant dystrophic epidermolysis bullosa using polymerase chain reaction amplification of segments of COL7A1, followed by heteroduplex analysis. Examination of the polymerase chain reaction corresponding to exon 73 revealed a heteroduplex resulting from a G-to-A transition at nucleotide 6127 in the triple-helical domain of COL7A1, which conve rted a glycine residue to an arginine (G2043R). The dominant dystrophi c epidermolysis bullosa phenotype in this family probably arose becaus e of a dominant negative effect of this mutation in COL7A1, resulting in the formation of structurally abnormal anchoring fibrils.