RECURRENT MUTATIONS IN THE TYPE-VII COLLAGEN GENE (COL7A1) IN PATIENTS WITH RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Mutations in the type VII collagen gene (COL7A1) are known to underlie different forms of the inherited blistering skin disease dystrophic e pidermolysis bullosa (DEB), Most COL7A1 mutations are unique to indivi dual families, and therefore it is usually necessary to screen all 118 exons of the gene to determine the molecular pathology in a patient w ith DEB, This study aimed to identify any recurrent mutations in COL7A 1 that might be applicable to mutation-detection strategies in these p atients, Mutational analysis was undertaken in 23 British patients wit h autosomal recessive DEB using PCR amplification of genomic DNA follo wed by heteroduplex analysis, nucleotide sequencing, and restriction s ite analysis, Two recurrent mutations were identified: R578X (6 of 46 alleles) and 7786delG (7 of 46 alleles), Haplotype analysis revealed t hat the mutations existed on similar allelic backgrounds in different patients, consistent with propagation of common British ancestral hapl otypes, although R578X and 7786delG also have been described in DEB pa tients from other ethnic backgrounds, Given the high relative frequenc y of these two COL7A1 mutations, British patients with recessive DEB s hould be screened initially for these nucleotide changes by PCR amplif ication of genomic DNA and restriction analysis before more exhaustive screening of COL7A1.