PRENATAL DIAGNOSIS OF CYSTIC FIBROSIS (CF) USING LINKED DNA MARKERS AND MICROVILLAR INTESTINAL ENZYME ANALYSIS

We are performing prenatal diagnosis of CF in families with 1 in 4 risk using linked DNA markers and amniotic fluid microvillar incestinal enzyme (MIE) analysis. The probes and RFLPs used for DNA analysis are as follows: metH with MspI and TaqI: metD with TaqI and BanI; D7S8 with MspI and TaqI. Using these probes in over 100 couples at 1 in 4 risk, 77% were fully informative. We have studied 53 pregnancies with 1 in 4 risk using DNA alone in 11, DNA and MIE in 26, and MIE alone in 16. DNA samples were obtained by chorionic villus sampling in 13 cases and by amniocentesis in 24 cases. For the 26 cases studied by DNA and MIE, results of both tests were conclusive and in agreement for 20 cases, and one test was diagnostic in 4 of the remaining cases. In only 2 of the 53 cases studied, no adequate diagnosis was achieved, because the fetus was at 50% risk by DNA data and MIE analysis was inconclusive. For 13 pregnancies predicted to be affected, 7 were terminated, 5 were born affected and 1 is awaiting outcome. For 37 pregnancies predicted to be unaffected, 11 were born unaffected and 26 are awaiting outcome. Assuming a recombination fraction of 0.01 between CF and the DNA loci, molecular prenatal diagnosis for affected or unaffected status would be 96%, 98% or >99% accurate if the fetus is predicted to be affected, carrier or noncarrier respectively. Use of flanking DNA markers or combination with MIE analysis can increase accuracy to >99%.