Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations

Chaohong Wang; Junxiang Tang; Keting Tong; Daoqi Huang; Huayu Tu; Qingnan Li; Jiansheng Zhu

doi:10.1186/s12920-021-01131-6

Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations

BMC Med Genomics. 2021 Dec 11;14(1):292. doi: 10.1186/s12920-021-01131-6.

Authors

Chaohong Wang¹, Junxiang Tang¹, Keting Tong¹, Daoqi Huang¹, Huayu Tu¹, Qingnan Li², Jiansheng Zhu³

Affiliations

¹ Affiliated Maternity and Child Health Hospital of Anhui Medical University, Maternity and Child Health Hospital of Anhui Province, Hefei, China.
² Beijing Genomics Institute, Beijing, China.
³ Affiliated Maternity and Child Health Hospital of Anhui Medical University, Maternity and Child Health Hospital of Anhui Province, Hefei, China. 26321650@qq.com.

Abstract

Purpose: The aim of this study was to assess the detection efficiency and clinical application value of non-invasive prenatal testing (NIPT) for foetal copy number variants (CNVs) in clinical samples from 39,002 prospective cases.

Methods: A total of 39,002 pregnant women who received NIPT by next-generation sequencing (NGS) with a sequencing depth of 6 M reads in our centre from January 2018 to April 2020 were enrolled. Chromosomal microarray analysis (CMA) was further used to diagnose suspected chromosomal aneuploidies and chromosomal microdeletion/microduplication for consistency assessment.

Results: A total of 473 pregnancies (1.213%) were positive for clinically significant foetal chromosome abnormalities by NIPT. This group comprised 99 trisomy 21 (T21, 0.254%), 30 trisomy 18 (T18, 0.077%), 25 trisomy 13 (T13, 0.064%), 155 sex chromosome aneuploidy (SCA, 0.398%), 69 rare trisomy (0.177%), and 95 microdeletion/microduplication syndrome (MMS, 0.244%) cases. Based on follow-up tests, the positive predictive values (PPVs) for the T21, T18, T13, SCA, rare trisomy, and MMS cases were calculated to be 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively. In addition, the PPVs of CNVs of < 5 Mb, 5-10 Mb, and > 10 Mb were 54.55%, 38.46%, and 40.00%, respectively. Among the 95 cases with suspected CNVs, 25 were diagnosed as true positive and 26 cases as false positive; follow-up prenatal diagnosis by CMA was not performed for 44 cases. Moreover, among the 25 true positive cases, 10 were pathogenic, 3 were likely pathogenic, and 12 were of uncertain significance.

Conclusion: NIPT is not only suitable for screening T21, T18, T13, and SCA but also has potential significance for CNV detection. As combined with ultrasound, extended NIPT is effective for screening MMS. However, NIPT should not be recommended for whole-chromosome aneuploidy screening.

Keywords: Chromosomal aneuploidy; Chromosomal microarray analysis (CMA); Chromosomal microdeletion/microduplication; Copy number variation (CNV); Non-invasive prenatal testing (NIPT).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aneuploidy
Chromosomes
DNA Copy Number Variations*
Female
Humans
Noninvasive Prenatal Testing*
Pregnancy
Prenatal Diagnosis