alexa Synergy of total PLAC4 RNA concentration and measurement of the RNA single-nucleotide polymorphism allelic ratio for the noninvasive prenatal detection of trisomy 21.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Tsui NB, Akolekar R, Chiu RW, Chow KC, Leung TY,

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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. This article was published in Clin Chem and referenced in Journal of Molecular and Genetic Medicine

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