ORIGINAL RESEARCH article
Front. Med.
Sec. Obstetrics and Gynecology
Early Non-Invasive Epigenetic Approach for Assessing Trisomy Risk in Maternal Plasma
Provisionally accepted
- 1Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India
- 2Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS),, Lucknow, India
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ABSTRACT Background: Karyotyping is the standard confirmatory test for identifying chromosomal abnormalities such as Trisomy 21, which requires amniotic fluid from pregnant women. The present study investigated the potential of methylated cell-free DNA (mcf-DNA) and methylated extracellular vesicle-derived DNA (mev-DNA) as an early, non-invasive epigenetic approach, specifically focusing on fetal-specific methylated regions (FSMRs) of RASSF1A, ERG, and UMODL1 (U1 & U2) to assess Trisomy 21 risk in maternal plasma. Methods: Blood samples were collected from pregnant women (n=120) between 10th and 24th weeks of gestation who were at higher risk for Trisomy 21. Three out of 120 were found positive for Trisomy 21 through Amniocentesis. Moreover, mcf-DNA and mev-DNA were isolated from Trisomy positive and age-matched healthy pregnant (n=8) and non-pregnant women (n=8). FSMRs were analyzed using qPCR to compare the cycle threshold (Ct) values. Gene copy number analysis was performed using the plasmid standards method to assess Trisomy detection sensitivity. Results: Trisomy pregnancies had significantly lower mean Ct values for RASSF1A and UMODL1 (U1 & U2) in both mcf-DNA and mev-DNA compared to healthy pregnancies, and this was further confirmed by higher copy numbers in trisomy pregnancies than in healthy pregnancies. Moreover, the gene copy number in mcf-DNA was significantly higher than mev-DNA for the RASSF1A, ERG, and UMODL1 (U1 & U2) genes in trisomy pregnancies. Conclusion: This pilot study demonstrates the feasibility of using mcf-DNA and mev-DNA for detecting Trisomy 21-associated fetal methylation signatures in maternal plasma. While consistent with earlier findings, these results validate the applicability of methylated DNA immunoprecipitation (MeDIP) based qPCR methylation assays in a North Indian cohort and support their potential integration into population-specific non-invasive prenatal screening strategies.
Keywords: and Trisomy, epigenetic markers, extracellular vesicles derived DNA, Free fetal DNA, methylated cell-free DNA
Received: 12 Sep 2025; Accepted: 13 Jan 2026.
Copyright: © 2026 Katiyar, Srivastava, Mishra, Phadke and Tiwari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Suman Mishra
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