NOVEL GLYCINE SUBSTITUTION MUTATIONS IN COL7A1 REVEAL THAT THE PASINIAND COCKAYNE-TOURAINE VARIANTS OF DOMINANT DYSTROPHIC EPIDERMOLYSIS-BULLOSA ARE ALLELIC

Mutations in the type VII collagen gene (COL7A1) have been shown to un derlie dystrophic epidermolysis bullosa (DEB), The dominantly inherite d forms of DEB have been divided into two clinical subcategories, the Pasini (DDEB-P) and the Cockayne-Touraine (DDEB-CT) variants, on the b asis of the presence or absence of albopapuloid lesions, In this study , we have examined the molecular basis of DDEB in two Japanese familie s, one with DDEB-P and the other with DDEB-CT, Mutation detection stra tegy consisted of polymerase chain reaction amplification of COL7A1 fr om genomic DNA, followed by heteroduplex analysis and direct-nucleotid e sequencing, The results revealed heterozygous glycine substitution m utations, G2076D and G2033R, in these families, respectively, Thus, th ese two variants of DDEB are allelic, and subtle differences in the cl inical presentation may reflect the precise position of the mutation a long the type VII collagen molecule. Alternatively, the nature of the substituting amino acid (D versus R) may influence the clinical phenot ype. This is the first demonstration of a COL7A1 mutation in DDEB-P, a nd brings the total number of dominant DEB variants with underlying gl ycine substitutions in COL7A1 to five, including the pretibial and loc alized variants as well as the Bart's syndrome, in addition to DDEB-P and DDEB-CT.