Efficiency of noninvasive prenatal testing for the detection of fetal microdeletions and microduplications in autosomal chromosomes

Pei, Yuanyuan; Hu, Liang; Liu, Jin-Xing; Wen, Liang; Luo, Xian; Lü, Jian; Wei, Fengxiang

doi:10.1002/mgg3.1339

Cited by 24 publications

(32 citation statements)

References 20 publications

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“…In the detection of CNV by using NIPT, 104 samples were detected, among which, 18 were true positive, with a PPV of 32.14%, and 38 were false positive. NIPT has certain detection efficacy for detecting CNV, but there are still many false positive cases, and the results still need further validation by karyotype analysis or CMA testing [ 28 , 29 ], which is especially important for cases with pathogenic or potentially pathogenic CNV. However, despite the higher chance of false positives for CNV using NIPT, since it is difficult to detect CNV below 10 Mb by conventional karyotype analysis, NIPT can compensate for the deficiency of karyotype analysis and reduce the missed diagnosis caused by visual judgment.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Chaohong²,

Tang³

et al. 2021

Mol Cytogenet

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Objective To assess the detection efficiency of noninvasive prenatal testing (NIPT) for fetal autosomal aneuploidy, sex chromosome aneuploidy (SCA), other chromosome aneuploidy, copy number variation (CNV), and to provide further data for clinical application of NIPT. Materials and methods 25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected, and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid, with some samples subjected to further validation by chromosomal microarray analysis, and followed up for pregnancy outcome. Results A total of 25,517 pregnant women who received NIPT, 25,502 cases were tested successfully, and 294 high-risk samples (1.15%) were detected, there were 96 true positive samples, 117 false positive samples and 81 cases were refused further diagnosis. Samples with high risk of autosomal aneuploidy were detected in 71 cases (0.28%), and 51 cases were confirmed, including: trisomy 21 (T21) in 44 cases, trisomy 18 (T18) in 5 cases, and trisomy 13 (T13) in 2 cases; the positive predictive value (PPV) was 91.67%, 45.45%, and 33.33%, respectively, and the negative predictive value was 100%, the false positive rate (FPR) was 0.02%, 0.02%, and 0.02%, respectively.13 samples with high risk of mosaic trisomies 21, 18, and 13 were detected, and 1 case of T21mos was confirmed with a PPV of 8.33%. Samples with high risk of SCA were detected in 72 cases (0.28%), and the diagnosis was confirmed in 23 cases, with a PPV of 41.07% and a FPR of 0.13%. These included 3 cases of 45,X, 6 cases of 47,XXY, 8 cases of 47,XXX and 6 cases of 47,XYY, with PPVs of 12.00%, 50.00%, 72.73%, and 75.00%, respectively, and false-positive rates of 0.09%, 0.02%, 0.01% and 0.01% respectively. Samples with high risk of CNV were detected in 104 cases (0.41%) and confirmed in 18 cases, with a PPV of 32.14% and a FPR of 0.15%. Samples with high risk of other chromosomal aneuploidy were detected in 34 cases (0.13%), and the diagnosis was confirmed in 3 cases, which were T2, T9, and T16 respectively. The overall PPV for other chromosome aneuploidy was 12.50%, with a FPR of 0.08%. Conclusion NIPT is indicated for trisomies 21, 18 and 13 screening, especially for T21. It also has some certain reference value for SCA and CNV, but is not recommended for screening of other chromosomal aneuploidy.

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Section: Discussionmentioning

confidence: 99%

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Chaohong²,

Tang³

et al. 2021

Mol Cytogenet

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“…It also has the potential to detect foetal CNVs, but with false-positive and false-negative results. Recent studies have showed that the accuracy of NIPT for CNVs is still unsatisfactory and needs to be improved [ 20 , 21 ]. CMA is still the most effective method for CNVs detection.…”

Section: Discussionmentioning

confidence: 99%

Prenatal chromosomal microarray analysis in foetuses with isolated absent or hypoplastic nasal bone

Shi

Lü

et al. 2022

Annals of Medicine

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Objectives To evaluate the efficiency of chromosomal microarray analysis (CMA) in the prenatal diagnosis of foetuses with isolated absent or hypoplastic nasal bone (NB) in the first and second trimester. Methods From January 2015 to April 2021, foetuses with isolated absent or hypoplastic NB who received invasive prenatal diagnosis were enrolled. The results of CMA were analysed Results There were 221 foetuses, including 166 cases with isolated absent NB and 55 cases with isolated hypoplastic NB. Twenty-four foetuses (10.9%, 24/221) had an ultrasonic diagnosis in the first trimester and 197 (89.1%, 197/221) had a ultrasonic diagnosis in the second trimester. The overall diagnostic yield of CMA was 9.0% (20/221). Aneuploidies were detected in 13 (5.9%, 13/221) foetuses, including 10 Down syndrome, 2 Klinefelter's syndrome and 1 trisomy 18. Pathogenic copy number variations (CNVs) were detected in seven foetuses (3.2%, 7/221). In addition, variants of unknown significance (VOUS) were detected in four foetuses. The foetuses with isolated absent NB had a higher detection rate of chromosome abnormality than the isolated hypoplastic NB, but the difference was not significant in the statistical analysis (10.2% vs. 5.5%, χ 2 =0.642, p = .423). No significant difference was observed in the detection rate between the first trimester and the second trimester (16.6% vs. 8.1%, χ 2 = 1.002, p = .317, Chi-square test). Conclusion CMA can increase the diagnostic yield of chromosome abnormality, especially pathogenic CNVs for foetuses with isolated absent or hypoplastic NB. CMA should be recommended when isolated absent or hypoplastic NB is suspected antenatally.7

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“…More recently, some laboratories have expanded NIPS to detect CNVs. [ 2 , 3 ] However, false positives caused by the influence of mother, fetus or placenta simultaneously exist due to limitations of the technology. In a retrospective study of 8152 pregnant women, they analyzed the subchromosomal microdeletions and microduplications, and only 13 (36.11%) of the 51 positive cases (0.63%) were true positive.…”

Section: Discussionmentioning

confidence: 99%

“…However, due to low production of cell-free fetal DNA from placental origin or low sequencing depth, NIPS yields false negative and false positive results in the detection of CNVs. [ 2 ] Therefore, further diagnostic means is needed. CNV-seq is a high-resolution whole-genome screening technology that can be used to analyze the presence of CNVs.…”

Section: Introductionmentioning

confidence: 99%

Partial trisomy 16q and partial monosomy 7p of a fetus derivated from paternal balanced translocation

Xie

Liu²,

Zhang³

et al. 2021

Medicine

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Introduction: Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation. Patient concern: This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation. Diagnoses: The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father. Interventions: No treatment for the fetus. Outcomes: Pregnancy was terminated. Conclusions: To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS.

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Efficiency of noninvasive prenatal testing for the detection of fetal microdeletions and microduplications in autosomal chromosomes

Cited by 24 publications

References 20 publications

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases

Prenatal chromosomal microarray analysis in foetuses with isolated absent or hypoplastic nasal bone

Partial trisomy 16q and partial monosomy 7p of a fetus derivated from paternal balanced translocation

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