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Non-invasive prenatal testing of trisomy 18 by an epigenetic marker in first trimester maternal plasma.

Lee da E, Kim SY, Lim JH, Park SY, Ryu HM - PLoS ONE (2013)

Bottom Line: The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells.Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001).Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001).

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.

ABSTRACT

Background: Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.

Methodology/principal findings: A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.

Conclusions: Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.

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Related in: MedlinePlus

ROC curves of U-maspin and M-maspin concentrations.The ROC curves of U-maspin and M-maspin concentrations are represented by red and blue lines, respectively.
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pone-0078136-g004: ROC curves of U-maspin and M-maspin concentrations.The ROC curves of U-maspin and M-maspin concentrations are represented by red and blue lines, respectively.

Mentions: To evaluate the accuracy of this approach for non-invasive detection of fetal trisomy 18, ROC curve analyses were performed for each factor (Fig. 4). The AUCs of U-maspin and M-maspin concentrations were 0.98 (95% CI: 0.95–1.01) with a standard error (SE) of 0.02 and 0.91 (95% CI: 0.79–1.02) with a SE of 0.06, respectively (P<0.001 for both). The optimal cutoff value for each factor was set at 90.9% sensitivity, as determined by ROC analysis. The U-maspin cutoff concentration of 19.2 copies/mL had a sensitivity of 90.9%, specificity of 96.4%, PPV of 83.3%, and NPV of 98.1% for identifying women carrying a trisomy 18 fetus from women carrying a normal fetus. The M-maspin cutoff concentration of 31.5 copies/mL had a sensitivity of 90.9%, specificity of 74.5%, PPV of 41.7%, and NPV of 97.6% (Table 3).


Non-invasive prenatal testing of trisomy 18 by an epigenetic marker in first trimester maternal plasma.

Lee da E, Kim SY, Lim JH, Park SY, Ryu HM - PLoS ONE (2013)

ROC curves of U-maspin and M-maspin concentrations.The ROC curves of U-maspin and M-maspin concentrations are represented by red and blue lines, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815335&req=5

pone-0078136-g004: ROC curves of U-maspin and M-maspin concentrations.The ROC curves of U-maspin and M-maspin concentrations are represented by red and blue lines, respectively.
Mentions: To evaluate the accuracy of this approach for non-invasive detection of fetal trisomy 18, ROC curve analyses were performed for each factor (Fig. 4). The AUCs of U-maspin and M-maspin concentrations were 0.98 (95% CI: 0.95–1.01) with a standard error (SE) of 0.02 and 0.91 (95% CI: 0.79–1.02) with a SE of 0.06, respectively (P<0.001 for both). The optimal cutoff value for each factor was set at 90.9% sensitivity, as determined by ROC analysis. The U-maspin cutoff concentration of 19.2 copies/mL had a sensitivity of 90.9%, specificity of 96.4%, PPV of 83.3%, and NPV of 98.1% for identifying women carrying a trisomy 18 fetus from women carrying a normal fetus. The M-maspin cutoff concentration of 31.5 copies/mL had a sensitivity of 90.9%, specificity of 74.5%, PPV of 41.7%, and NPV of 97.6% (Table 3).

Bottom Line: The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells.Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001).Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001).

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.

ABSTRACT

Background: Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.

Methodology/principal findings: A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.

Conclusions: Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.

Show MeSH
Related in: MedlinePlus