title: Novel glycine substitution mutations in COL7A1 reveal that the Pasini and Cockayne-Touraine variants of dominant dystrophic epidermolysis bullosa are allelic.
abstract: Mutations in the type VII collagen gene (COL7A1) have been shown to underlie dystrophic epidermolysis bullosa (DEB). The dominantly inherited forms of DEB have been divided into two clinical subcategories, the Pasini (DDEB-P) and the Cockayne-Touraine (DDEB-CT) variants, on the basis of the presence or absence of albopapuloid lesions. In this study, we have examined the molecular basis of DDEB in two Japanese families, one with DDEB-P and the other with DDEB-CT. Mutation detection strategy consisted of polymerase chain reaction amplification of COL7A1 from genomic DNA, followed by heteroduplex analysis and direct nucleotide sequencing. The results revealed heterozygous glycine substitution mutations, G2076D and G2034R, in these families, respectively. Thus, these two variants of DDEB are allelic, and subtle differences in the clinical presentation may reflect the precise position of the mutation along the type VII collagen molecule. Alternatively, the nature of the substituting amino acid (D versus R) may influence the clinical phenotype. This is the first demonstration of a COL7A1 mutation in DDEB-P, and brings the total number of dominant DEB variants with underlying glycine substitutions in COL7A1 to five, including the pretibial and localized variants as well as the Bart's syndrome, in addition to DDEB-P and DDEB-CT.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kon
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: D
authors.initials: D
authors.lastname: Sawamura
authors.forename: I
authors.initials: I
authors.lastname: Hashimoto
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000328:Adult; D000483:Alleles; D003094:Collagen / Q000235:genetics*; D019281:Dimerization; D016108:Epidermolysis Bullosa Dystrophica / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D014644:Genetic Variation; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D010375:Pedigree; D017354:Point Mutation
chemical_list: D009692:Nucleic Acid Heteroduplexes; D003094:Collagen; D005998:Glycine