PREMATURE TERMINATION CODONS ON BOTH ALLELES OF THE TYPE-VII COLLAGENGENE (COL7A1) IN 3 BROTHERS WITH RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Epidermolysis bullosa (EB) is a group of heritable mechano-bullous ski n diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membra ne zone. In the most severe, dystrophic (scarring) forms of EB, bliste rs form below the cutaneous basement membrane at the level of the anch oring fibrils, which are composed of type VII collagen, Ultrastructura l observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candid ate gene in the dystrophic forms of EB. We have recently cloned the en tire cDNA and the gene for human COL7A1. In this study, we describe di stinct mutations in both COL7A1 alleles in three brothers with severe, mutilating recessive dystrophic EB (the Hallopeau-Siemens type, HS-RD EB). The patients are compound heterozygotes for two different mutatio ns, both of which result in a premature termination codon in COL7A1, a nd the parents mere shown to be clinically heterozygous carriers of th e respective mutations. Premature termination codons in both alleles o f COL7A1 appear to be the underlying cause of severe, recessive dystro phic EB in this family.