PRENATAL-DIAGNOSIS OF COLLAGEN DISORDERS BY DIRECT BIOCHEMICAL-ANALYSIS OF CHORIONIC VILLUS BIOPSIES

We have developed a method for early prenatal diagnosis of molecular d isorders of collagens I and III. The method takes advantage of the fac t that isolated chorionic villi contain significant amounts of collage ns in their extracellular matrix (stroma) and that they synthesize col lagens in vitro. After metabolic labeling of chorion villus biopsies i n tote with radioactive amino acids, collagens are extracted and analy zed by SDS-PAGE. Direct staining of the gel shows collagens synthesize d in vivo, whereas autoradiofluorography identifies collagens synthesi zed during incubation in vitro. Unlike collagens synthesized by cultur ed amniotic fluid cells, collagens extracted from chorionic villi are not overmodified and thus allow better identification of molecular def ects. Results are available within 3 to 5 d after biopsy. Using this m ethod, we have correctly excluded Ehlers-Danlos syndrome type IV in tw o pregnancies, Ehlers-Danlos syndrome type VII in one pregnancy, and l ethal osteogenesis imperfecta in four pregnancies. In addition, we cor rectly predicted a healthy fetus and an embryo affected with lethal os teogenesis imperfecta in consecutive pregnancies from a couple in whic h the asymptomatic mother was a somatic mosaic for a COL1A1 G-to-A tra nsition (Gly355Asp). Direct collagen analysis of chorion villus biopsi es labeled in toto is rapid and reliable and may become the method of choice for the prenatal diagnosis of selected collagen disorders.