title: Prenatal diagnosis in known fragile X carriers.
abstract: Prenatal diagnosis for fragile X syndrome was performed in 34 pregnancies of 33 known carriers, on 22 chorionic villus samples (CVS), and 15 amniocentesis samples. Fetal and maternal DNA were analyzed by the EagI/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 with 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 premutation and a small full mutation. Of 8 mothers with full mutations, the fetal results were 5 full, 2 normal, and 1 premutation (whose mother was a full/pre compound heterozygote). Of 26 mothers with premutations, the fetal results were 5 full, 13 normal, 7 premutation, and 1 uninterpretable (maternal contamination). Maternal premutations were sized in kb by Southern blot and in CGG repeat number by PCR; the predicted correlation between maternal length and penetrance was seen. Follow-up studies include 3 full mutations and 2 premutations confirmed by DNA analysis at birth. Maternal contamination of CVS samples was encountered in 3 of 22 cases, illustrating the value of EagI in detecting maternal (lyonized) chromosomes.
authors.affiliation: Genetics & IVF Institute, Fairfax, Virginia 22031.
authors.forename: A
authors.initials: A
authors.lastname: Maddalena
authors.forename: B D
authors.initials: BD
authors.lastname: Hicks
authors.forename: W C
authors.initials: WC
authors.lastname: Spence
authors.forename: G
authors.initials: G
authors.lastname: Levinson
authors.forename: P N
authors.initials: PN
authors.lastname: Howard-Peebles
mesh_terms: D000649:Amniocentesis; D015139:Blotting, Southern; D015193:Chorionic Villi Sampling; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D015342:DNA Probes; D015246:Deoxyribonuclease EcoRI; D015252:Deoxyribonucleases, Type II Site-Specific; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D008297:Male; D008745:Methylation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004247:DNA; D015342:DNA Probes; D015246:Deoxyribonuclease EcoRI; D015252:Deoxyribonucleases, Type II Site-Specific; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide; C046751:endodeoxyribonuclease XmaIII