PRENATAL-DIAGNOSIS OF CONGENITAL ADRENAL-HYPERPLASIA DUE TO 21-HYDROXYLASE DEFICIENCY BY ALLELE-SPECIFIC HYBRIDIZATION AND SOUTHERN BLOT

The feasibility and accuracy of gene-specific molecular genetic diagno sis for congenital adrenal hyperplasia due to 21-hydroxylase deficienc y was studied in a group of 24 pregnancies at 25% risk of carrying an affected fetus. Chorionic villus sampling was performed at 9-10 weeks' gestation. Southern analysis and polymerase chain reaction, followed by allele-specific hybridization for a panel of nine known mutations, were performed for each family. Mutations were identified in 95% of ch romosomes examined; the molecular diagnosis was accurate in 96% of inf ants as confirmed by postnatal examination. The most common mutation i dentified was an A-to-G transition at base 656 in the second intron, t he result of an apparent gene conversion. In one family, there had bee n a de novo mutation in intron 2, which was detected in the proband, b ut not in the mother or in the fetus. We conclude that first trimester prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydrox ylase deficiency is feasible and accurate employing CYP21-specific pro bes.