Open AccessSystematic analysis of the causes of NIPS sex chromosome aneuploidy false‐positive results
Author(s) -
Lyu Zhaoru,
Huang Chunhong
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1963
Subject(s) - aneuploidy , false positive paradox , chromosome , copy number variation , fetus , karyotype , false positive rate , cell free fetal dna , biology , obstetrics , pregnancy , medicine , genetics , prenatal diagnosis , gene , genome , statistics , mathematics , machine learning , computer science
Objective To investigate the underlying causes of false positives in NIPT of fetal sex chromosomal aneuploidies using fetal cell‐free DNA from maternal plasma. Methods In the present study, we focus on a cohort of 23,984 pregnancy cases with NIPT. Karyotyping and FISH analysis were employed to verify the NIPT detected false‐positive results of fetal sex chromosomal aneuploidies, and a comparative CNV sequencing on positive and negative NIPT cases was uniquely performed to elucidate the underlying causes. Results A total of 166 cases (0.69%) were identified as fetal sex chromosomal abnormalities, while 84 cases were found to be false‐positive results possibly associated with maternal X chromosomal aneuploidies ( n = 8), maternal X chromosomal structural abnormalities ( n = 1), maternal CNVs ( n = 4) as well as known placental mosaicism ( n = 1). Furthermore, our study showed that the maternal chromosome CNV between 1–1.6 Mb was associated with false‐positive NIPT results in sex chromosomal abnormalities. Conclusion Our research demonstrated the spectrum of factors causing false positives in NIPT of fetal sex chromosomal abnormalities based on a large cohort. The effective maternal CNV size cut‐off identified in our study could integrate into bioinformatics algorithms for reducing the false‐positive rate, however, further investigation is necessary to confirm this.