scholarly journals Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 26
Author(s):  
Zhaochen Bai ◽  
Hu Zhao ◽  
Shaobin Lin ◽  
Linhuan Huang ◽  
Zhiming He ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Clinical Settings ◽  
Str Analysis ◽  
Forensic Research ◽  
Combined Use ◽  
Prenatal Test ◽  
Mz Twins ◽  
Twin Pregnancies ◽  
Fetal Fraction

As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.

scholarly journals Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex

2016 ◽  
Vol 62 (6) ◽  
pp. 848-855 ◽  
Author(s):  
George Koumbaris ◽  
Elena Kypri ◽  
Kyriakos Tsangaras ◽  
Achilleas Achilleos ◽  
Petros Mina ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Dna Analysis ◽  
Prenatal Testing ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Trisomy 13 ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genomic Regions ◽  
Fetal Fraction

Abstract BACKGROUND There is great need for the development of highly accurate cost effective technologies that could facilitate the widespread adoption of noninvasive prenatal testing (NIPT). METHODS We developed an assay based on the targeted analysis of cell-free DNA for the detection of fetal aneuploidies of chromosomes 21, 18, and 13. This method enabled the capture and analysis of selected genomic regions of interest. An advanced fetal fraction estimation and aneuploidy determination algorithm was also developed. This assay allowed for accurate counting and assessment of chromosomal regions of interest. The analytical performance of the assay was evaluated in a blind study of 631 samples derived from pregnancies of at least 10 weeks of gestation that had also undergone invasive testing. RESULTS Our blind study exhibited 100% diagnostic sensitivity and specificity and correctly classified 52/52 (95% CI, 93.2%–100%) cases of trisomy 21, 16/16 (95% CI, 79.4%–100%) cases of trisomy 18, 5/5 (95% CI, 47.8%–100%) cases of trisomy 13, and 538/538 (95% CI, 99.3%–100%) normal cases. The test also correctly identified fetal sex in all cases (95% CI, 99.4%–100%). One sample failed prespecified assay quality control criteria, and 19 samples were nonreportable because of low fetal fraction. CONCLUSIONS The extent to which free fetal DNA testing can be applied as a universal screening tool for trisomy 21, 18, and 13 depends mainly on assay accuracy and cost. Cell-free DNA analysis of targeted genomic regions in maternal plasma enables accurate and cost-effective noninvasive fetal aneuploidy detection, which is critical for widespread adoption of NIPT.

scholarly journals Performance of non-invasive prenatal testing for foetal chromosomal abnormalities in 1048 twin pregnancies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuan Cheng ◽  
Xinran Lu ◽  
Junxiang Tang ◽  
Jingran Li ◽  
Yuxiu Sun ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
False Negative ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Clinical Value ◽  
Non Invasive ◽  
Negative Results ◽  
Negative Case ◽  
Twin Pregnancies

Abstract Objective To investigate the clinical value of non-invasive prenatal testing (NIPT) to screen for chromosomal abnormalities in twin pregnancies and to provide further data on NIPT manifestations in twin pregnancies. Materials and methods In a 4-year period, 1048 women with twin pregnancies were voluntarily prospectively tested by NIPT to screen for chromosomal abnormalities by sequencing cell-free foetal DNA (cffDNA) in maternal plasma. Positive NIPT results were confirmed by karyotyping, while negative results were followed up 42 days after delivery. Results Thirteen women had positive NIPT results as follows: 2 cases of trisomy 21 (T21), 1 of trisomy 18 (T18), 7 of sex chromosome aneuploidy (SCA), 1 of microdeletion, and 2 of microduplication. Of these 13 cases, 2 were true-positive cases confirmed by foetal karyotype analysis, namely, 1 case of T21 and 1 of microdeletion. Furthermore, the remaining 11 high-risk pregnant women were confirmed as false positive by foetal karyotyping. Thus, the combined positive predictive value (PPV) of NIPT screening for chromosomal abnormalities in twin pregnancies was 15.4% (2/13). There were no false-negative case via our follow-up results. Conclusion Safe and rapid NIPT has a certain clinical application value; however, the PPV is limited, and the screening efficiency is not stable. Careful use should be made in the screening of chromosomal abnormalities in twin pregnancies.

Non-invasive prenatal testing of pregnancies at risk for phenylketonuria

2018 ◽  
Vol 104 (1) ◽  
pp. F24-F29 ◽  
Author(s):  
Huikun Duan ◽  
Ning Liu ◽  
Zhenhua Zhao ◽  
Yiqian Liu ◽  
Yin Wang ◽  
...  
Keyword(s):  
Single Molecule ◽  
Phenylalanine Hydroxylase ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Correct Assignment ◽  
Highly Sensitive ◽  
Prenatal Test ◽  
Villus Cell ◽  
Compound Heterozygotes

BackgroundPhenylketonuria (PKU) is a common metabolic disorder caused predominately by mutations in the phenylalanine hydroxylase (PAH) gene. The aim of the study was to design and validate the performance of a non-invasive prenatal test (NIPT) for PKU using circulating single molecule amplification and resequencing technology (cSMART).MethodsA total of 18 couples at genetic risk for having a child with PKU were recruited to the study. Gold standard invasive prenatal diagnosis (IPD) was performed on amniocyte or villus cell DNA by Sanger sequencing, targeting the known parental PAH mutations. Retrospectively, NIPT was also performed on stored maternal plasma samples from the 18 pregnancies by a multiplex cSMART assay designed to target all known DNA variants in the PAH gene.ResultsBenchmarking against IPD results, NIPT correctly genotyped all fetuses, including six compound heterozygotes with PKU, four normal non-carriers of PKU and eight heterozygote carriers of PKU comprising five cases of a maternally inherited mutation and three cases of a paternally inherited mutation.ConclusionsThe NIPT cSMART PKU assay was highly sensitive and specific for mutation detection and correct assignment of fetal genotypes. Based on comprehensive mutation coverage across the PAH gene, the assay may initially have clinical utility as a pregnancy screening test for high-risk carrier couples.

scholarly journals Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 569
Author(s):  
Michaela Hyblova ◽  
Maria Harsanyova ◽  
Diana Nikulenkov-Grochova ◽  
Jitka Kadlecova ◽  
Marcel Kucharik ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Detection Algorithm ◽  
Detection Sensitivity ◽  
Clinical Settings ◽  
Noninvasive Prenatal Testing ◽  
Low Pass ◽  
Cnv Detection ◽  
Fetal Fraction

Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.

Yearly Changes in Stillbirth Rates of Zygotic Twins in Japan, 1975-1994

1998 ◽  
Vol 47 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Y. Imaizumi ◽  
K. Nonaka
Keyword(s):  
Medical Care ◽  
Twin Pregnancy ◽  
Japanese Women ◽  
Stillbirth Rate ◽  
Monochorionic Twin ◽  
Mz Twins ◽  
Twin Pregnancies

AbstractThe stillbirth rates decreased to 2/3 for MZ male twins, 1/2 for MZ female twins, and under 1/2 for DZ twins for both sexes during the 19-year period from 1975 in Japan. The stillbirth rate was significantly higher in MZ males than MZ females in each year, whereas stillbirth rates of DZ twins for both sexes indicated similar values during that period. After 1986, stillbirth rates were more than 2 times higher in MZ twins than in singletons and in DZ twins. The higher stillbirth rate of MZ twins as opposed to DZ twins could be related to monochorionic twin pairs in MZ twins. The stillbirth rate decreased more drastically in twins for both zygosities than in singleton births during the 34-year period from 1960. However, declining rates of stillbirths may be attributed to medical care during twin pregnancies. Recommendation of an optimum day to give birth for twin pregnancy is 37-38 weeks for Japanese women.

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

2021 ◽  
pp. 1-9
Author(s):  
Yunfang Shi ◽  
Xiaozhou Li ◽  
Duan Ju ◽  
Yan Li ◽  
Xiuling Zhang ◽  
...  
Keyword(s):  
Screening Tool ◽  
Sex Chromosome ◽  
Diagnostic Testing ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Chromosome Abnormalities ◽  
Noninvasive Prenatal Testing ◽  
Sex Chromosome Abnormalities ◽  
Sex Chromosome Aneuploidies ◽  
Mosaic Karyotype

<b><i>Objective:</i></b> This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. <b><i>Methods:</i></b> This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. <b><i>Results:</i></b> After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (<i>n</i> = 42), 47,XXX (<i>n</i> = 20), 47,XYY (<i>n</i> = 16), and 45,X (<i>n</i> = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. <b><i>Conclusion:</i></b> NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.

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