PRENATAL-DIAGNOSIS IN KNOWN FRAGILE-X CARRIERS

Prenatal diagnosis for fragile X syndrome was performed in 34 pregnanc ies of 33 known carriers, on 22 chorionic villus samples (CVS), and 15 amniocentesis samples. Fetal and maternal DNA were analyzed by the Ea gI/EcoRI Southern blot of Rousseau et al. [1991: N Engl J Med 325:1673 -1681], with detection of full mutations ensured by a second loading w ith brief electrophoresis. As a supplemental assay for full mutations, cytogenetic induction was performed in 20 cases. Positive cytogenetic results were helpful in confirming full mutations in CVS cases where the fetal DNA was intermediate in appearance, between a large premutat ion and a small full mutation. Of 8 mothers with full mutations, the f etal results were 5 full, 2 normal, and 1 premutation (whose mother wa s a full/pre compound heterozygote). Of 26 mothers with premutations, the fetal results were 5 full, 13 normal, 7 premutation, and 1 uninter pretable (maternal contamination). Maternal premutations were sized in kb by Southern blot and in CGG; repeat number by PCR; the predicted c orrelation between maternal length and penetrance was seen. Follow-up studies include 3 full mutations and 2 premutations confirmed by DNA a nalysis at birth. Maternal contamination of CVS samples was encountere d in 3 of 22 cases, illustrating the value of EagI in detecting matern al (lyonized) chromosomes. (c) 1994 Wiley-Liss, Inc.