Genetic basis of Bart's syndrome: A glycine substitution mutation in the type VII collagen gene

Bart's syndrome was initially described as a genodermatosis characterized by congenital localized absence of the skin, together with blistering and nail abnormalities. Recent analysis of Bart's original kindred demonstrated ultrastructural abnormalities in the anchoring fibrils and linkage of the inheritance of the disease to the region of chromosome 3 near the type VII collagen gene (COL7A1). We have performed mutation analysis in this family by using electrophoretic heteroduplex analysis followed by direct nucleotide sequencing of DNA. These results disclosed a G-to-A transition within exon 73 of COL7A1, which results in a glycine-to-arginine substitution within the triple-helical domain of type VII collagen in affected individuals. In this family, these findings demonstrate that Bart's syndrome is a clinical variant of dominant dystrophic epidermolysis bullosa.