Synergy of total PLAC4 RNA concentration and measurement of the RNA single-nucleotide polymorphism allelic ratio for the noninvasive prenatal detection of trisomy 21.
نویسندگان
چکیده
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.
منابع مشابه
Explore the dynamic alternation of gene PLAC4 mRNA expression levels in maternal plasma in second trimester for nonivasive detection of trisomy 21
OBJECTIVE Noninvasive prenatal detection of trisomy 21 (T21) has been achieved by measuring the ratio of two alleles of a single nucleotide polymorphism in circulating placenta specific 4 (PLAC4) mRNA in maternal plasma with a few assays in recent years. Our research is to explore the variations of PLAC4 mRNA expression level in maternal plasma with normal pregnancies in second trimester, which...
متن کامل44 single-nucleotide polymorphisms expressed by placental RNA: assessment for use in noninvasive prenatal diagnosis of trisomy 21.
To the Editor: For noninvasive prenatal diagnosis, markers that directly reflect changes in chromosome dosage are preferred over indirect markers that are associated with epiphenomena (1, 2). The RNA:single-nucleotide polymorphism (SNP) allelic ratio strategy was described recently as a means to directly assess fetal chromosome dosage in maternal plasma (2). Quantitive comparison of the allelic...
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Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally t...
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ورودعنوان ژورنال:
- Clinical chemistry
دوره 56 1 شماره
صفحات -
تاریخ انتشار 2010