Advancing Non-Invasive Prenatal Screening: A Targeted 1069-Gene Panel for Comprehensive Detection of Monogenic Disorders and Copy Number Variations.

UNLABELLED

We introduce an innovative, non-invasive prenatal screening approach for detecting fetal monogenic alterations and copy number variations (CNVs) from maternal blood.

METHOD

Circulating free DNA (cfDNA) was extracted from maternal peripheral blood and processed using the VeriSeq NIPT Solution (Illumina, San Diego, CA, USA), with shallow whole-genome sequencing (sWGS) performed on a NextSeq550Dx (Illumina). A customized gene panel and bioinformatics tool, named the "VERA Revolution", were developed to detect variants and CNVs in cfDNA samples. Results were compared with genomic DNA (gDNA) extracted from fetal samples, including amniotic fluid and chorionic villus sampling and buccal swabs.

RESULTS

The study included pregnant women with gestational ages from 10 + 3 to 15 + 2 weeks (mean: 12.1 weeks). The fetal fraction (FF), a crucial measure of cfDNA test reliability, ranged from 5% to 20%, ensuring adequate DNA amount for analysis. Among 36 families tested, 14 showed a wild-type genotype. Identified variants included two deletions (22q11.2, and 4p16.3), two duplications (16p13 and 5p15), and eighteen single-nucleotide variants (one in , three in , three in one in , one in , one in , one in , one in , one in , two in and three in ). Significant concordance was found between our panel results and prenatal/postnatal genetic profiles.

CONCLUSIONS

The "VERA Revolution" test highlights advancements in prenatal genomic screening, offering potential improvements in prenatal care.