Application of droplet digital PCR for prenatal screening of Down syndrome

摘要

Packground: This study was proposed to explore the feasibility of droplet digital PCR (ddPCR) analysis for non-invasive prenatal gnosis of Down syndrome. Materials and Methods: The authors studied maternal plasma samples from 465 pregnant women car-ng euploid and trisomy 21 (T21) fetuses. A methylation-sensitive restriction endonuclease, BstUI, was used to digest the hy- netethylated holocarboxylase synthetase (HLCS) gene. The authors quantified digestion-resistant HLCS gene on chromosome 21 and al-specific rs6636 SNP allele on chromosome 14 by droplet digital PCR analysis. Maternal plasma DNA analysis was performed by nparing the ratio of hypermethylatcd HLCS to fetal-specific rs6636 SNP allele between two groups. Results: Using a rs6636 SNP le on chromosome 14 as the reference marker, the authors analyzed 78 euploid and 28 T21 plasma samples. The ratios of the num-s of positive hypermethylatcd HLCS and the fetal-specific C allele in the euploid and T21 samples were significantly different (p <1, Mann-Whitney rank sum test), all but two samples with the fetal-specific C allele were correctly classified, while the ratios of the bers of positive hypermethylated HLCS and the fetal-specific G allele in the euploid and T21 samples were significantly different 0.01, Mann-Whitney rank sum test); all but one sample with the fetal-specific C allele were correctly classified. Conclusions: The y demonstrated that ddPCR approach can be applied for prenatal screening of trisomy 21.