scholarly journals Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy

2019 ◽  
Vol 8 (7) ◽  
pp. 937 ◽  
Author(s):  
Errol R. Norwitz ◽  
Gabriel McNeill ◽  
Akshita Kalyan ◽  
Elizabeth Rivers ◽  
Ebad Ahmed ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Monozygotic Twins ◽  
Maternal Plasma ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Fetal Sex ◽  
Non Invasive ◽  
Prenatal Test ◽  
Blinded Study ◽  
The Mean

We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome complements, fetal sex was evaluated by evaluating Y-chromosome loci, and aneuploidy was assessed through SNP ratios. Zygosity was correctly predicted in 100% of cases (93/93; 95% confidence interval (CI) 96.1%–100%). Individual fetal sex for both twins was also called with 100% accuracy (102/102; 95% weighted CI 95.2%–100%). All cases with copy number truth were also correctly identified. The dizygotic aneuploidy sensitivity was 100% (10/10; 95% CI 69.2%–100%), and overall specificity was 100% (96/96; 95% weighted CI, 94.8%–100%). The mean fetal fraction (FF) of monozygotic twins (n = 43) was 13.0% (standard deviation (SD), 4.5%); for dizygotic twins (n = 79), the mean lower FF was 6.5% (SD, 3.1%) and the mean higher FF was 8.1% (SD, 3.5%). We conclude SNP-based NIPT for zygosity is of value when chorionicity is uncertain or anomalies are identified. Zygosity, fetal sex, and aneuploidy are complementary evaluations that can be carried out on the same specimen as early as 9 weeks’ gestation.

scholarly journals Synergy of Total PLAC4 RNA Concentration and Measurement of the RNA Single-Nucleotide Polymorphism Allelic Ratio for the Noninvasive Prenatal Detection of Trisomy 21

2010 ◽  
Vol 56 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Nancy BY Tsui ◽  
Ranjit Akolekar ◽  
Rossa WK Chiu ◽  
Katherine CK Chow ◽  
Tak Y Leung ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Real Time Pcr ◽  
Trisomy 21 ◽  
Digital Pcr ◽  
Maternal Plasma ◽  
Chromosome 21 ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Allelic Ratio ◽  
Mrna Concentration

Abstract Background: Maternal plasma mRNA encoded by the PLAC4 gene (placenta-specific 4), which is transcribed from chromosome 21 in placental cells, is a potential marker for the noninvasive assessment of chromosome 21 dosage in the fetus. We evaluated the diagnostic sensitivities and specificities of 2 trisomy 21–screening approaches that use maternal plasma PLAC4 mRNA. Methods: We studied maternal plasma samples from 153 pregnant women carrying euploid and trisomy 21 fetuses. For the samples in which the fetuses were heterozygous for the studied PLAC4 single-nucleotide polymorphism (SNP), we measured the ratio between 2 alleles of the SNP in maternal plasma PLAC4 mRNA (RNA-SNP) by mass spectrometric (MS) and digital PCR methods. For pregnancies involving fetuses homozygous for the SNP, we quantified the total PLAC4 mRNA concentration in maternal plasma by real-time PCR and digital PCR. Results: For the RNA-SNP approach, we achieved a diagnostic sensitivity and specificity of 100% (95% CI, 40.2%–100%) and 89.7% (95% CI, 78.8%–96.1%), respectively, for both the MS and the digital PCR methods. For the mRNA-quantification approach, the areas under the ROC curves were 0.859 (95% CI, 0.741–0.903) and 0.833 (95% CI, 0.770–0.923) for plasma PLAC4 mRNA concentrations measured by the real-time PCR and the digital PCR methods, respectively. Conclusions: For prenatal screening of trisomy 21, the quantification of the total PLAC4 mRNA concentration can be used in a synergistic manner with the RNA-SNP allelic ratio approach to increase the population coverage of cases in which diagnostic information can be obtained.

scholarly journals Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism–based noninvasive prenatal test

2015 ◽  
Vol 212 (1) ◽  
pp. 79.e1-79.e9 ◽  
Author(s):  
Kirsten J. Curnow ◽  
Louise Wilkins-Haug ◽  
Allison Ryan ◽  
Eser Kırkızlar ◽  
Melissa Stosic ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Prenatal Test ◽  
Twin Pregnancies

scholarly journals Differential DNA Methylation between Fetus and Mother as a Strategy for Detecting Fetal DNA in Maternal Plasma

2002 ◽  
Vol 48 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Leo LM Poon ◽  
Tse N Leung ◽  
Tze K Lau ◽  
Katherine CK Chow ◽  
YM Dennis Lo
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Direct Sequencing ◽  
Methylation Status ◽  
Maternal Plasma ◽  
Primer Extension ◽  
Nucleotide Polymorphism ◽  
Primer Extension Assay ◽  
Single Nucleotide ◽  
Epigenetic Markers ◽  
Fetal Dna

Abstract Background: Fetal DNA has been detected in maternal plasma by the use of genetic differences between mother and fetus. We explore the possibility of using epigenetic markers for the specific detection of fetal DNA in maternal plasma. Methods: A differentially methylated region in the human IGF2-H19 locus and a single-nucleotide polymorphism in this region were chosen for the study. The methylation status in this region is maintained in such a way that the paternal allele is methylated and the maternal allele is unmethylated. The single-nucleotide polymorphism was typed by direct sequencing of PCR products. The methylation status of this region was ascertained by bisulfite conversion and methylation-specific PCR. Differentially methylated fetal alleles were detected in maternal plasma by direct sequencing and a primer-extension assay. Results: Women in the second (n = 21; 17–21 weeks) and third (n = 18; 37–42 weeks) trimesters of pregnancy were recruited. Among these 39 volunteers, the 16 who were heterozygous for the single-nucleotide polymorphism were chosen for further analysis. In 11 of these 16 cases, paternally inherited methylated fetal alleles were different from the methylated alleles of the respective mothers. Using direct sequencing, we detected paternally inherited methylated fetal DNA in 6 of 11 (55%) cases. In 8 of the 16 heterozygous cases, the fetuses possessed an unmethylated maternally inherited allele that was different from the unmethylated allele of the mother. Using a primer-extension assay, we detected fetal-derived maternally inherited alleles in maternal plasma of four of eight (50%) cases. Conclusions: These results represent the first use of fetal epigenetic markers in noninvasive prenatal analysis. These data may also have implications for the investigation of other types of chimerism.

scholarly journals Non-Invasive Prenatal Detection of Trisomy 13 Using a Single Nucleotide Polymorphism- and Informatics-Based Approach

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96677 ◽  
Author(s):  
Megan P. Hall ◽  
Matthew Hill ◽  
Bernhard Zimmermann ◽  
Styrmir Sigurjonsson ◽  
Margaret Westemeyer ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Trisomy 13 ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Non Invasive ◽  
Prenatal Detection
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