PRENATAL-DIAGNOSIS OF CONGENITAL ADRENAL-HYPERPLASIA BY DIRECT DETECTION OF MUTATIONS IN THE STEROID 21-HYDROXYLASE GENE

OBJECTIVE Our aim was to develop a rapid and accurate method for the prenatal diagnosis of congenital adrenal hyperplasia using the polymerase chain reaction to detect mutations in the steroid 21-hydroxylase gene. These procedures will help to minimize exposure to dexamethasone treatment of either affected males or unaffected females. DESIGN AND PATIENTS Chorionic villus biopsy samples were obtained between 10 and 11 weeks gestation from three females carrying fetuses at risk of steroid 21-hydroxylase deficiency. Blood samples were taken from parents and the index case in each family. MEASUREMENTS Three common mutations in the 21-hydroxylase B gene were detected following DNA amplification. RESULTS Prenatal diagnosis of congenital adrenal hyperplasia was successful in all three cases. One affected female was treated with dexamethasone to term. In the other two cases, one affected male and one carrier also male, dexamethasone was withdrawn at an early stage. CONCLUSIONS First trimester prenatal diagnosis of steroid 21-hydroxylase deficiency was achieved in three pregnancies with a strategy based on direct detection of gene mutations.