Prenatal Samples and Methylation Patterns

We occasionally receive questions about whether our probemixes for methylation analysis, such as those focused on imprinting disorders, can be used on prenatal samples such as chorionic villi (CVS) or amniotic fluid. This is a valid question, as prenatal and postnatal tissues differ biologically from postnatal samples, and methylation patterns are known to be influenced by developmental stage, tissue origin, and cell composition. In prenatal testing, commonly used materials such as CVS and amniotic fluid originate from different fetal or extra-embryonic tissues and may contain heterogeneous cell populations, which can complicate the interpretation of epigenetic measurements.

MRC Holland has not validated the use of prenatal material for methylation analysis. However, several studies have highlighted the challenges inherent to using prenatal samples for methylation analysis:

• Methylation profiles in CVS and amniotic fluid might not reflect the actual epigenetic constitution of the fetus (Beygo et al. 2023; Eggermann et al. 2016; Paganini et al. 2015).
• Imprinting establishment can vary between loci and even within the same locus (Paganini et al. 2015).
• Culturing of CVS samples may alter methylation patterns in a locus-specific manner (Paganini et al. 2015).
• Uncultured amniotic fluid has been shown to yield more variable methylation ratios compared to blood (Gede et al. 2016).
• The timing of abnormal methylation events and the mosaic nature of imprinting disorders further complicate interpretation of results from prenatal material.

For these reasons, we do not recommend using MS-MLPA probemixes on prenatal samples. If you have questions about the suitability of certain sample types for use with a specific probemix, please consult the available product documentation or contact our technical support team by emailing info@mrcholland.com.