Pilot study of a novel multi‐functional noninvasive prenatal test on fetus aneuploidy, copy number variation, and single‐gene disorder screening

BACKGROUND: The noninvasive prenatal testing (NIPT) has been successfully used in the clinical screening of fetal trisomy 13, 18, and 21 in the last few years and researches on detecting sub-chromosomal copy number variations (CNVs) and monogenic diseases are also in progress. To date, multiple tests are needed in order to complete a full set of fetus disorder screening, which is costly and time consuming. Therefore, an integrated 3-in-1 NIPT approach will be in great demand by routine clinical practice in the near future. METHODS: We designed a target capture sequencing panel with an associate bioinformatics pipeline to create a novel multi-functional NIPT method and we evaluated its performance by testing 22 clinical samples containing aneuploidy, CNV, and single-gene disorder. Chromosomal aneuploidy and CNV were detected based on the Z-value approach, whereas single-gene disorder was identified by using the "pseudo-tetraploid" model to estimate the best-suited genotype for each locus. RESULTS: The performance of this newly constructed 3-in-1 system was promising. We achieved a 100% detection rate for chromosomal aneuploidies (7/7), a 100% diagnosis rate for fetus CNVs larger than 20 Mb (3/3), and an 86.4% accuracy for single-gene disorder screening (19/22). CONCLUSION: For the first time, we showed that it is possible to use just a single NIPT test to detect three distinct types of fetus disorder and laid a foundation for developing a cheaper, faster, and multi-functional NIPT method in the future.