(872) Validation and clinical case report in non invasive prenatal testing for all chromosomes

Objective: Whole-Genome Sequencing (WGS)-based bioinformatics algorithms have a potential advantage to detect the aneuploidies for all chromosomes. Despite this advantage, chromosome 21, 18, 13 and sex chromosome have typically been applied for Non-invasive prenatal testing (NIPT) and have sufficient validation results. As Rare Autosomal Trisomies (RATs) research helps the understanding of feto-placental biology, a detection algorithm with higher accuracy is also importantly required.

Study Design: We first searched for RAT cases from the literature and generated artificial data for each case, according to various fetal fraction. We used an in-house pipeline, which applied the z-score twice to maximize the sensitivity and set the threshold. Finally, we calculated the demographic statistics using clinical data.

Results: Depending on the fetal fraction, the accuracy varies for each chromosome. In most chromosomes, the proposed algorithm showed high accuracy ( > 99%) with 10% fetal fraction, and most of chromosomes had high accuracy ( > 95%) even at 5% fetal fraction, while chromosome 19 showed low accuracy as 80%. One hundred eighty-seven RATs were identified in 30,364 clinical samples, and Trisomy 7 (n=58) was the most frequent, followed by Trisomy16 (n=17), Trisomy 8 (n=16). Amniotic karyotyping was performed in 23 cases, with 6 confirming an abnormality (mosaic or trisomy). The other 17 cases were normal amniocentesis results, which may suggest confined placental mosaicism (CPM).

Conclusion: Our results show that we have developed an algorithm, with well-designed artificial samples for detecting all chromosomes aneuploidies. All chromosome testing can help to detect the presence of RATs that may adversely affect pregnancy outcomes, with respect to placental dysfunction, fetal growth restriction and potential uniparental disomy (UPD).