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Sci China Life Sci. 2019 Feb;62(2):215-224. doi: 10.1007/s11427-017-9344-7. Epub 2018 Aug 2.

Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women.

Yao H1, Gao Y2,3,4, Zhao J2,3, Zhang R1, Xu H2, Hu H1, Luo Y1, Yuan Y5, Fu M5, Zhang H5, Jiang H2,3, Wang W2,4,5, Yang H2,6, Wang J2,6, Liang Z7, Chen F8,9,10.

Author information

1
Department of Gynecology & Obstetrics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China.
2
BGI-Shenzhen, Shenzhen, 518083, China.
3
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.
4
Birth Defect Screening Project Lab, BGI-Shenzhen, Shenzhen, 518083, China.
5
Clinical laboratories of BGI Health, BGI-Shenzhen, Shenzhen, 518083, China.
6
James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China.
7
Department of Gynecology & Obstetrics, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, China. zhi.lzliang@gmail.com.
8
BGI-Shenzhen, Shenzhen, 518083, China. fangchen@genomics.cn.
9
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. fangchen@genomics.cn.
10
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, DK-2100, Denmark. fangchen@genomics.cn.

Abstract

Cell-free DNA (cfDNA) testing for common fetal trisomies (T21, T18, T13) is highly effective. However, the usefulness of cfDNA testing in detecting other chromosomal abnormalities is unclear. We evaluated the performance of cfDNA testing for genome-wide abnormalities, and analyzed the incremental yield by reporting extra abnormalities. We performed genome-wide cfDNA testing in 15,626 consecutive pregnancies prospectively enrolled in this study. cfDNA testing results were reported and counseling was given depending on the presence of extra chromosomal abnormalities. cfDNA testing identified 190 cases (1.2%) of chromosomal abnormalities including 100 common trisomies and 90 additional abnormalities. By expanding the cfDNA reporting range to genome-wide abnormalities, the false positive rate increased to 0.39% (P<0.001) and positive predictive value (PPV) was reduced to 65.58% (P=0.42). However, the detection yield increased from 0.44% to 0.65% (P=0.014), and cfDNA testing detected 38.61% (39/101) additional abnormalities with no ultrasound and biochemical screening findings. cfDNA testing outperformed biochemical screening by showing 60 times higher true positive rate and fewer false negative results. Genome-wide cfDNA testing significantly increased the diagnostic yield by detecting extra abnormalities, especially those without diagnostic indications. Genome-wide cfDNA testing has fewer false positive and false negative results compared with biochemical screening.

KEYWORDS:

PPV; cell-free DNA; chromosomal abnormalities; genome-wide; sensitivity; specificity

PMID:
30076564
DOI:
10.1007/s11427-017-9344-7

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