Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa

The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelat ed patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules , and skin fragility. Mutation analysis using polymerase chain reaction amp lification of genomic DNA, heteroduplex analysis and direct nucleotide sequ encing demonstrated pathogenetic COL7A1 mutations in each case. Four patien ts had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R , G2369S, and G2713R), a fifth was a compound heterozygote for a splice sit e mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (68 63del16), This study shows that the molecular pathology in patients with th e distinctive clinical features of epidermolysis bullosa pruriginosa is het erogeneous and suggests that other factors, in addition to the inherent COL 7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginos a phenotype.