RAPID AND SIMPLE PRENATAL DNA DIAGNOSIS OF DOWNS-SYNDROME

Background Prenatal diagnosis of chromosomal abnormality requires cyto genetic analysis of amniotic fetal cells. The necessary culture time d elays diagnosis, is expensive, and requires substantial scientific exp ertise. In a masked prospective study, we investigated the feasibility of PCR amplification of chromosome 21 markers for the prenatal diagno sis of Down's syndrome. Methods The study population consisted of 2167 pregnant women, undergoing amniocentesis for prenatal diagnosis. In t his cohort at least 1.5 mL amniotic fluid was available surplus to the requirements for traditional diagnostic methods. DNA was extracted fr om the surplus amniotic fluid and amplified in fluorescence-based PCR reactions, with three small-tandem-repeat markers located on chromosom e 21. The products of the reactions were analysed on a DNA sequencer t o identify the presence of two or three copies of chromosome 21. Findi ngs In 2083 (97.4%) of 2139 samples of amniotic fluid that were not ma croscopically blood-stained, two DNA markers gave an informative and c orrect result, identifying 2053 fetuses as normal and 30 as having tri somy 21 Down's syndrome (as confirmed by cytogenetic analysis). An ext ra marker was informative in 32 of 41 other clear samples. Thus a tota l of 99.6% informative results was achieved with these three markers. Macroscopically bloodstained samples (28 [1.3%]) were unsuitable for D NA testing. They gave a typical but non-informative result. There were no false-positive or false-negative results. Interpretation The PCR-b ased DNA diagnostic test has great potential for improved prenatal dia gnosis of Down's syndrome, with the advantage that results may be avai lable within a day.