Recurrent molecular abnormalities in type VII collagen in southern Italian patients with recessive dystrophic epidermolysis bullosa

In this study we searched for mutations in the type VII collagen gene (COL7A1) in 10 families from Southern Italy with severe generalized recessive dystrophic epidermolysis bullosa using PCR amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing. Our principal aim was to identify any recurrent mutations in COL7A1 that might facilitate future mutation detection strategies in this population. Three recurrent COL7A1 mutations were delineated in six of the 10 families: a frameshift mutation in exon 4, 497insA, was detected in three affected individuals from three families, a deletion mutation at the acceptor splice site of intron 114/exon 115, 8441-14de121, was found in five patients in three of the families, and an intron 49 acceptor splice site mutation, 4783-1 G-to-A, was identified in three subjects in two families (GenBank accession no, L02870). Haplotype analyses showed evidence for propagation of common ancestral mutant COL7A1 alleles for each of these recurrent mutations. These results contribute significantly to understanding the nature of COL7A1 pathology in patients from Southern Italy and in designing future approaches to mutation detection.