A recurrent COL7A1 mutation, R2814X, in British patients with recessive dystrophic epidermolysis bullosa

Mutations in the type VII collagen gene, COL7A1, underlie all forms of dyst rophic epidermolysis bullosa (DEB). The identification of COL7A1 mutations in DEB is complicated because the COL7A1 gene contains 118 distinct exons a nd most mutations are specific to individual families. In an attempt to sim plify mutation screening procedures we searched for recurrent mutations in genomic DNA from 38 British patients with recessive DEB using polymerase ch ain reaction (PCR), heteroduplex analysis and direct nucleotide sequencing. We identified a recurrent premature termination codon, R2814X, on three ou t of 76 alleles, Previously we identified the COL7A1 mutations R578X and 77 86delG as other frequent molecular abnormalities in British recessive DEB p atients. Taken together, these three mutations account for approximate to 2 5% of the molecular pathology of this disease in our population discovered thus far and we recommend initial screening for these mutations by PCR and restriction analysis before undertaking more exhaustive COL7A1 gene analysi s. Such an approach is likely to reveal underlying COL7A1 mutations in a si gnificant number of cases.