Rapid Prenatal Detection of Down and Edwards Syndromes by Fluorescent Polymerase Chain Reaction with Short Tandem Repeat Markers

Chromosome analysis is the main tool for the prenatal diagnosis of trisomies but requires great technical expertise and time consuming manual procedures. Recently, alternative methods, which provide rapidity and accuracy, without culture, have been developed for pregnant women requiring rapid decisions for termination. In this study, multiplex fluorescent polymerase chain reactions (F-PCRs) were performed by the concurrent use of short tandem repeat (STR) markers specific for the chromosomes 18 and 21. The aims of this investigation were to evaluate the clinical usefulness of this assay for rapid prenatal detection of Down and Edwards syndromes and then to accumulate the basic data for clinical application. F-PCRs were carried out using DNA extracted from amniotic fluid and peripheral blood derived from 47 normal karyotypes, 23 Down and 8 Edwards syndrome patients. Fluorescent intensities of the PCR products were then calculated. Normal samples displayed diallelic peaks for each STR marker. Reference ranges of peak area ratios were 1.0 - 1.4 for D21S11, 1.0 - 1.5 for D21S1412 and 1.0 - 1.3 for D18S535 and D18S51. Down and Edwards syndromes showed characteristic triallelic peaks of similar intensity corresponding to 3 different alleles or characteristic diallelic peaks. The sensitivity, specificity and efficiency of the assay for detecting Down and Edwards syndromes were 96.7%, 93.6% and 94.8%, respectively. In conclusion, these results show that F-PCR rapidly detects Down and Edwards syndromes with high accuracy and provides normal reference ranges of peak area ratios. However, the presence of false results (4 out of 77 cases) and the possibility of anomalies other than trisomies 21 and 18 do not permit F-PCR to substitute for chromosome analysis.