scholarly journals Cell‐based noninvasive prenatal testing (cbNIPT) detects pathogenic copy number variations

2020 ◽  
Vol 8 (12) ◽  
pp. 2561-2567
Author(s):  
Lotte Hatt ◽  
Ripudaman Singh ◽  
Rikke Christensen ◽  
Katarina Ravn ◽  
Inga B Christensen ◽  
...  
Keyword(s):  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Noninvasive Prenatal Testing

scholarly journals Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Parental Willingness

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

Contribution of maternal copy number variations to false-positive fetal trisomies detected by noninvasive prenatal testing

2017 ◽  
Vol 37 (4) ◽  
pp. 318-322 ◽  
Author(s):  
Xiya Zhou ◽  
Lili Sui ◽  
Yalan Xu ◽  
Yijun Song ◽  
Qingwei Qi ◽  
...  
Keyword(s):  
False Positive ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Noninvasive Prenatal Testing

scholarly journals Copy number variant detection with low-coverage whole-genome sequencing is a viable replacement for the traditional array-CGH

2020 ◽  
Author(s):  
Marcel Kucharik ◽  
Jaroslav Budis ◽  
Michaela Hyblova ◽  
Gabriel Minarik ◽  
Tomas Szemes
Keyword(s):  
In Silico ◽  
Copy Number ◽  
Normal Population ◽  
Genetic Disorders ◽  
Prenatal Testing ◽  
In Silico Analysis ◽  
Copy Number Variant ◽  
Detection Algorithm ◽  
Copy Number Variations ◽  
Cnv Detection

Copy number variations (CNVs) are a type of structural variant involving alterations in the number of copies of specific regions of DNA, which can either be deleted or duplicated. CNVs contribute substantially to normal population variability; however, abnormal CNVs cause numerous genetic disorders. Nowadays, several methods for CNV detection are used, from the conventional cytogenetic analysis through microarray-based methods (aCGH) to next-generation sequencing (NGS). We present GenomeScreen - NGS based CNV detection method based on a previously described CNV detection algorithm used for non-invasive prenatal testing (NIPT). We determined theoretical limits of its accuracy and confirmed it with extensive in-silico study and already genotyped samples. Theoretically, at least 6M uniquely mapped reads are required to detect CNV with a length of 100 kilobases (kb) or more with high confidence (Z-score > 7). In practice, the in-silico analysis showed the requirement at least 8M to obtain >99% accuracy (for 100 kb deviations). We compared GenomeScreen with one of the currently used aCGH methods in diagnostic laboratories, which has a 200 kb mean resolution. GenomeScreen and aCGH both detected 59 deviations, GenomeScreen furthermore detected 134 other (usually) smaller variations. Furthermore, the overall cost per sample is about 2-3x lower in the case of GenomeScreen.

scholarly journals Parental willing to take invasive diagnosis after Expanded Noninvasive Prenatal Testing (expanded NIPT) in a cohort of 24768 cases

2020 ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Copy Number Variations ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Prenatal Test ◽  
Xyy Syndrome ◽  
Chromosomal Aneuploidies

Abstract BackgroundThe main aims of the study were to investigate the performance of expanded noninvasive prenatal test (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs) and copy number variations (CNVs) and parental willing to taking invasive prenatal diagnosis after expanded NIPT in China.ResultsOf the 24,736 cases, successful follow-up was conducted in 92.2% (411/446) cases. The sensitivity of expanded NIPT test was 98.61%,90.91% and 100% and specificity was 99.91%,99.95% and 99.87% for the detection of trisomies 21, 18 and 13 respectively. Expanded NIPT detected 45, XO, 47, XXX, 47, XXY, XYY syndrome, RATs and CNVs with positive predictive values of 57.39%, 19.61%, 75%, 79.41%, 77.78%, 10% and 56.25% respectively. The women carrying fetuses with T21/T18/T13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those positive for SCAs, RATs and CNVs.ConclusionsOur study demonstrates that the expanded NIPT detects fetal trisomies 21,18 and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs and CNVs is still relatively poor and needed to be improved. With a positive expanded NIPT result, the women at high risk for common trisomies are more willing to take invasive prenatal diagnosis and terminate their pregnancies.* the first two authors contribute equally to this study.

scholarly journals A Novel Graphic-Aided Algorithm (gNIPT) Improves the Accuracy of Noninvasive Prenatal Testing

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qingwen Zhu ◽  
Jing Wang ◽  
Xiaoning Xu ◽  
Shiying Zhou ◽  
Zhengli Liao ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
False Negative ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Negative Control ◽  
Trisomy 13 ◽  
Singleton Pregnancy ◽  
Noninvasive Prenatal Testing ◽  
Number Variation

Noninvasive Prenatal Testing (NIPT) has advanced the detection of fetal chromosomal aneuploidy by analyzing cell-free DNA in peripheral maternal blood. The statistic Z-test that it utilizes, which measures the deviation of each chromosome dosage from its negative control, is now widely accepted in clinical practice. However, when a chromosome has loss and gain regions which offset each other in the z-score calculation, merely using the Z-test for the result tends to be erroneous. To improve the performance of NIPT in this aspect, a novel graphic-aided algorithm (gNIPT) that requires no extra experiment procedures is reported in this study. In addition to the Z-test, this method provides a detailed analysis of each chromosome by dividing each chromosome into multiple 2 Mb size windows, calculating the z-score and copy number variation of each window, and visualizing the z-scores for each chromosome in a line chart. Data from 13537 singleton pregnancy women were analyzed and compared using both the normal NIPT (nNIPT) analysis and the gNIPT method. The gNIPT method had significantly improved the overall positive predictive value (PPV) of nNIPT (88.14% vs. 68.00%, p=0.0041) and the PPV for trisomy 21 (T21) detection (93.02% vs. 71.43%, p=0.0037). There were no significant differences between gNIPT and nNIPT in PPV for trisomy 18 (T18) detection (88.89% vs. 63.64%, p=0.1974) and in PPV for trisomy 13 (T13) detection (57.14% vs. 50.00%, p=0.8004). One false-negative T18 case in nNIPT was detected by gNIPT, which demonstrates the potency of gNIPT in discerning chromosomes that have variation in multiple regions with an offsetting effect in z-score calculation. The gNIPT was also able to detect copy number variation (CNV) in chromosomes, and one case with pathogenic CNV was detected during the study. With no additional test requirement, gNIPT presents a reasonable solution in improving the accuracy of normal NIPT.

scholarly journals Optical Genome Mapping as a Next-Generation Cytogenomic Tool for Detection of Structural and Copy Number Variations for Prenatal Genomic Analyses

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 398
Author(s):  
Nikhil Shri Sahajpal ◽  
Hayk Barseghyan ◽  
Ravindra Kolhe ◽  
Alex Hastie ◽  
Alka Chaubey
Keyword(s):  
Copy Number ◽  
Southern Blotting ◽  
Genome Mapping ◽  
Genetic Disorders ◽  
Prenatal Testing ◽  
Standard Of Care ◽  
Copy Number Variations ◽  
Repeat Expansion ◽  
Chromosomal Microarray ◽  
Next Generation

Global medical associations (ACOG, ISUOG, ACMG) recommend diagnostic prenatal testing for the detection and prevention of genetic disorders. Historically, cytogenetic methods such as karyotype analysis, fluorescent in situ hybridization (FISH) and chromosomal microarray (CMA) are utilized worldwide to diagnose common syndromes. However, the limitations of each of these methods, either performed in tandem or simultaneously, demonstrates the need of a revolutionary technology that can alleviate the need for multiple technologies. Optical genome mapping (OGM) is a novel method that fills this void by being able to detect all classes of structural variations (SVs), including copy number variations (CNVs). OGM is being adopted by laboratories as a tool for both postnatal constitutional genetic disorders and hematological malignancies. This commentary highlights the potential for OGM to become a standard of care in prenatal genetic testing based on its capability to comprehensively identify large balanced and unbalanced SVs (currently the strength of karyotyping and metaphase FISH), CNVs (by CMA), repeat contraction disorders (by Southern blotting) and multiple repeat expansion disorders (by PCR-based methods or Southern blotting). Next-generation sequencing (NGS) methods are excellent at detecting sequence variants, but they are unable to accurately resolve repeat regions of the genome, which limits their ability to detect all classes of SVs. Notably, multiple molecular methods are used to identify repeat expansion and contraction disorders in routine clinical laboratories around the world. With non-invasive prenatal testing (NIPT) becoming the standard of care screening assay for all global pregnancies, we anticipate that OGM can provide a high-resolution, cytogenomic assay to be employed following a positive NIPT screen or for high-risk pregnancies with an abnormal ultrasound. Accurate detection of all types of genetic disorders by OGM, such as liveborn aneuploidies, sex chromosome anomalies, microdeletion/microduplication syndromes, repeat expansion/contraction disorders is key to reducing the global burden of genetic disorders.

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