At least 35 cases of prenatal fra(X) diagnosis have been confirmed and reported. Amniotic fluid, fetal blood and chorion -ic villus samples have exhibited fra(X)(q27.3) in cultures from 26 males and 9 females. Here we have detected fra(X) in female and male amniotic fluid specimens, AF1/fra(X),X and AF2(X),Y, respectively, and a male CVS/fra(X),Y using both FUdR and excess thymidine (THY) to demonstrate the marker chromosome. Both FUdR and THY detected fra(X) and usually FUdR was superior to THY with the exception of placental cultures. It was important to examine more than one culture per protocol since no fra(X) was observed in one AF2 FUdR culture while another exhibited 19.2% expression. Similarly, confirmation studies in lung fibroblast cultures for AF2 exhibited 4.3% fra(X) in one lab while another found negative results. A similar observation in whole blood cultures was also made recently by us. In addition, we have recently experienced our first false negative fra(X),X prenatal diagnosis. We have observed another case where only one cell in 300 exhibited fra(X) where the male fetus was 50% at-risk and was referred to us after the 20th week of gestation by sonography. On the basis of our experience we recommend the following: 1) the excess THY fra(X) induction system is effective but not superior to FUdR; 2) at least two duplicate cultures per induction system should be analyzed for the marker chromosome to avoid the possibility of false-negative diagnosis; 3) where fra(X) is not demonstrated or is present in very low frequencies in CVS and/or amniotic fluid cultures, complementary DNA marker studies and/or fetal blood cultures must be made available; 4) gestational age dating by ultrasonography is recommended as early as possible.
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