An assessment of the analytical performance of non‐invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717‐patient sample in a single prenatal diagnosis Centre in China

Luo, Yanmei; Hu, Huamei; Zhang, Rong; Ma, Yanlin; Pan, Yan; Yang, Lei; Hu, Bin; Yao, Hong; Liang, Zhiqing

doi:10.1002/jgm.3362

Cited by 18 publications

(17 citation statements)

References 36 publications

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“…The PPV of NIPT in sex chromosomes trisomy was consistent with the report of Suo et al ( 2018 ) on 47,XXX, 47,XXY, and 47,XYY. The PPV of 45,X was consistent with the results reported by Kornman et al ( 2018 ), and was lower than those of which reported by Suo et al ( 2018 ), Persico et al ( 2016 ), Porreco et al ( 2014 ), Song et al ( 2013 ), and Luo et al ( 2021 ). The lower PPV of 45,X might also be related to the fact that a greater number of 45,X fetuses have abnormal ultrasonic structures than other types of SCA fetuses, so their parents tend to forgo diagnosis and proceed to the termination.…”

Section: Discussionsupporting

confidence: 90%

Systematic analysis of the causes of NIPS sex chromosome aneuploidy false‐positive results

Lyu

Huang

2022

Molec Gen & Gen Med

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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.

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Section: Discussionsupporting

confidence: 90%

Systematic analysis of the causes of NIPS sex chromosome aneuploidy false‐positive results

Lyu

Huang

2022

Molec Gen & Gen Med

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“…During the last decade, cfNIPT has been introduced worldwide as an efficient screening tool for detection of trisomies 13, 18, and 21 and potentially sex chromosomes, however, the positive predictive value for the SCAs is lower (Gadsbøll et al, 2020;Luo et al, 2021;Pertile et al, 2021). Prenatal diagnosis of SCAs in a fetus is complicated by the absence of confirmatory ultrasound findings beyond the increased nuchal translucency (Christiansen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Jeppesen

Hatt²,

Singh³

et al. 2021

Front. Genet.

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Background: Cell-free NIPT and cell-based NIPT are risk-free testing options using maternal blood samples to screen for fetal aneuploidies, but the methods differ. For cell-free NIPT, the fetal fraction of cell-free DNA in plasma is analyzed with a high background of maternal DNA. In contrast, for cell-based NIPT, a limited number of the rare, intact fetal cells are isolated for the genetic analysis. This case demonstrates the differences regarding testing for fetal sex-chromosomes anomalies (SCAs) between these two tests.Materials and Methods: A pregnant woman with mosaicism for Turner syndrome opted for NIPT in first trimester. For the cell-free NIPT analysis, DNA extraction, genome-wide massive parallel sequencing, and data analysis were carried out as described by the kit manufacturer (Illumina©, San Diego, CA, USA). For cell-based NIPT, the first sample gave no result, but the woman consented to repeat cell-based NIPT. After whole genome amplification and STR analysis, fetal DNA from three individual fetal cells was subjected to chromosomal microarray (aCGH, Agilent oligoarray, 180 kb).Results: Fetal fraction was 7%, and cell-free NIPT showed 2 copies of chromosomes 13, 18, and 21 and a decreased proportion of chromosome X, suggestive of fetal Turner syndrome. In contrast, the cell-based NIPT result showed no aneuploidy and two X-chromosomes in the fetus.Conclusion: cell-based NIPT may provide a non-invasive testing option to screen for SCAs in women with mosaicism for monosomy-X in blood, where cell-free NIPT cannot discriminate whether the X-loss is maternal or fetal.

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“…However, the positive predictive value (PPV) for detection of 45,X by cfDNA screening is much lower than for trisomy 21, ranging from 9% to 40%, and various factors limit its performance. [20][21][22][23][24][25][26] Confined placental mosaicism (CPM) and true fetal mosaicism are more common for monosomy X than for other chromosomal abnormalities. 27 The performance of cfDNA testing for SCA can also be affected by undiagnosed maternal sex chromosome abnormalities, such as X-chromosome deletions or mosaic Xchromosome aneuploidy, including the well-described somatic maternal loss of the second X chromosome with increasing maternal age.…”

Section: Introductionmentioning

confidence: 99%

Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

et al. 2023

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Objective We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell‐free DNA (cfDNA) screening results for monosomy X. Methods From a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X‐chromosome variant. Results We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high‐risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X‐chromosome variants. All 16 fetuses with high‐risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with “variant” karyotypes had different anomalies. Conclusion Both, 45,X or X‐chromosome variants can be detected after a high‐risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X‐chromosome variant.

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An assessment of the analytical performance of non‐invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717‐patient sample in a single prenatal diagnosis Centre in China

Cited by 18 publications

References 36 publications

Systematic analysis of the causes of NIPS sex chromosome aneuploidy false‐positive results

Systematic analysis of the causes of NIPS sex chromosome aneuploidy false‐positive results

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

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