PubMed1996
A 28-year-old woman, who previously had had a child affected with the hereditary blistering skin disorder, recessive dystrophic epidermolysis bullosa, presented at 7 weeks' gestation for prenatal diagnosis. Genomic DNA, obtained from her, her husband (who is a first cousin), their unaffected child, and their previously affected child, was used to screen all 118 exons of the type VII collagen gene (COL7A1) by polymerase chain reaction (PCR) amplification followed by heteroduplex analysis of the PCR products. Established common polymorphisms within the NC-1 region of COL7A1 were informative for both the normal maternal and paternal alleles. In addition, a putative homozygous mutation, a G to C transversion at nucleotide position 7708, was identified in the affected child. This substitution converts a glycine residue (GGT) within the Gly-X-Y region of the type VII collagen triple helix into an arginine residue (CGT), and leads to the creation of a new MnlI restriction site. Both parents and the healthy sibling were shown to be clinically normal heterozygous carriers of this mutation. A chorionic villus biopsy was performed at 10 weeks' gestation and DNA was extracted from the villi. Assessment of informative intragenic markers, and the putative mutation, revealed that the fetus had inherited both the normal maternal and paternal COL7A1 alleles. Thus, first trimester DNA-based prenatal diagnosis predicts that this child is neither affected with recessive dystrophic epidermolysis bullosa, nor is an unaffected carrier of this genodermatosis.