Identification of universal mRNA markers for noninvasive prenatal screening of trisomies

Objective: The discovery of placental transcripts in peripheral blood of pregnant women prompted us toinvestigate which was the most appropriate biological specimen, between plasma and serum, to easily detect them and to exploit hPL (human placental lactogen), βhCG (human chorionic gonadotrophin β-subunit), LOC90625, and TFPI2 (tissue factor pathway inhibitor 2) levels in order to establish whether an abnormal variation degree of presence of these placental transcripts are likely to be associated to specific fetal trisomies. Method: RNA was extracted from plasma and serum samples of 255 pregnant women bearing euploid fetuses,17 bearing fetuses affected by trisomy 21 and 10 with fetuses affected by trisomy 18. Placental transcript analysis was performed by real time RT-PCR using relative quantification. Results: Results obtained from euploid samples showed that fetal transcripts were more abundant in plasma than in serum samples. Euploid samples had a placental transcript abundance distinguishable from those withtrisomy 21 but not from those with trisomy 18. In particular, high βhCG abundance and advanced maternal age were significantly associated with trisomy 21 pregnancy. Conclusion: Plasma was the most suitable tool to be employed in the detection and dosage of placental transcripts. βhCG transcript together with maternal age could be a potential marker for noninvasive prenatal screening of fetal trisomy 21. Copyright  2010 John Wiley & Sons, Ltd. Key words: mRNA markers; noninvasive prenatal screening; placental transcripts; real time PCR; trisomy.