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 dystrophic epidermolysis bullosa (DEB). The identification of COL7A1 mutations in DEB is complicated because the COL7A1 gene contains 118 distinct exons and most mutations are specific to individual families. In an attempt to simplify mutation screening procedures we searched for recurrent mutations in genomic DNA from 38 British patients with recessive DEB using polymerase chain reaction (PCR), heteroduplex analysis and direct nucleotide sequencing. We identified a recurrent premature termination codon, R2814X, on three out of 76 alleles. Previously we identified the COL7A1 mutations R5 78X and 7786delG as other frequent molecular abnormalities in British recessive DEB patients. Taken together, these three mutations account for ≃ 25% 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 analysis. Such an approach is likely to reveal underlying COL7A1 mutations in a significant number of cases.