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

In this study we searched for mutations in the type VII collagen gene (COL7 A1) in 10 families from Southern Italy with severe generalised recessive dy strophic epidermolysis bullosa using PCR amplification of genomic DNA, hete roduplex analysis and direct nucleotide sequencing. Our principal aim was t o identify any recurrent mutations in COL7A1 that might facilitate: future mutation detection strategies in this population. Three recurrent COL7A1 mu tations were delineated in six of the 10 families: a frameshift mutation in exon 4, 497insA, was detected in three affected individuals from three fam ilies, a deletion mutation at the acceptor splice site of intron 114/exon 1 15, 8441-14del21, was found in live patients in three of the families, and an intron 49 acceptor splice site mutation, 4783-1 G-to-A, was identified i n 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 sig nificantly to understanding the nature of COL7A1 pathology in patients from Southern Italy and in designing future approaches to mutation detection.