PRENATAL-DIAGNOSIS FOR RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA IN 10 FAMILIES BY MUTATION AND HAPLOTYPE ANALYSIS IN THE TYPE-VII COLLAGEN GENE (COL7A1)

Background: Epidermolysis bullosa (EB) is a group of heritable disease s that manifest as blistering and erosions of the skin and mucous memb ranes. In the dystrophic forms of EB (DEB), the diagnostic hallmark is abnormalities in the anchoring fibrils, attachment structures beneath the cutaneous basement membrane zone. The major component of anchorin g fibrils is type VII collagen, and DEB has been linked to the type VI I collagen gene (COL7A1) at 3p21, with no evidence for locus heterogen eity. Due to life-threatening complications and significant long-term morbidity associated with the severe, mutilating form of recessive dys trophic EB (RDEB), there has been a demand for prenatal diagnosis from families with affected offspring. Materials and Methods: Intragenic p olymorphisms in COL7A1 and flanking microsatellite markers on chromoso me 3p21, as well as detection of pathogenetic mutations in families, w ere used to perform PCR-based prenatal diagnosis from DNA obtained by chorionic villus sampling at 10-15 weeks or amniocentesis at 12-15 wee ks gestation in 10 families at risk for recurrence of RDEB. Results: I n nine cases, the fetus was predicted to be normal or a clinically una ffected carrier of a mutation in one allele. These predictions have be en validated in nine cases by the birth of a healthy child. In one cas e, an affected fetus was predicted, and the diagnosis was confirmed by fetal skin biopsy. Conclusions: DNA-based prenatal diagnosis of RDEB offers an early, expedient method of testing which will largely replac e the previously available invasive fetal skin biopsy at 18-20 weeks g estation.