Journal
GENETICS IN MEDICINE
Volume 21, Issue 9, Pages 1998-2006Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41436-019-0467-4
Keywords
noninvasive prenatal screening; copy-number variation (CNV); 22q11.2 microdeletions; positive predictive value (PPV); microdeletion/microduplication syndromes (MMS)
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Funding
- National Key R&D Program of China [2017YFC1001800/02, 2016YFC0905100/02]
- National Natural Science Foundation of China [81571450]
- Key R&D Program of Hunan Province [2017SK2153]
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Purpose: To assess the clinical performance of an expanded noninvasive prenatal screening (NIPS) test (NIPS-Plus) for detection of both aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS). Methods: A total of 94,085 women with a singleton pregnancy were prospectively enrolled in the study. The cell-free plasma DNA was directly sequenced without intermediate amplification and fetal abnormalities identified using an improved copy-number variation (CNV) calling algorithm. Results: A total of 1128 pregnancies (1.2%) were scored positive for clinically significant fetal chromosome abnormalities. This comprised 965 aneuploidies (1.026%) and 163 (0.174%) MMS. From follow-up tests, the positive predictive values (PPVs) for T21, T18, T13, rare trisomies, and sex chromosome aneuploidies were calculated as 95%, 82%, 46%, 29%, and 47%, respectively. For known MMS (n = 32), PPVs were 93% (DiGeorge), 68% (22q11.22 microduplication), 75% (Prader-Willi/Angleman), and 50% (Cri du Chat). For the remaining genome-wide MMS (n = 88), combined PPVs were 32% (CNVs >= Mb) and 19% (CNVs <10 Mb). Conclusion: NIPS-Plus yielded high PPVs for common aneuploidies and DiGeorge syndrome, and moderate PPVs for other MMS. Our results present compelling evidence that NIPS-Plus can be used as a first-tier pregnancy screening method to improve detection rates of clinically significant fetal chromosome abnormalities.
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