Fetal Nucleic Acids in Maternal Plasma Toward the Development of Noninvasive Prenatal Diagnosis of Fetal Chromosomal Aneuploidies

Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 01/2008; 1137(1). DOI: 10.1196/annals.1448.004

ABSTRACT The discovery of cell-free fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Over the last few years, a number of approaches have been demonstrated to allow such circulating fetal nucleic acids to be used for the prenatal detection of chromosomal aneuploidies. One such approach involves the enrichment of fetal DNA, such as by size fractionation or by the contro- versial formaldehyde treatment technique. A second approach involves the targeting of fetal-specific nucleic acid molecules, including fetal-specific epigenetic markers and placenta-specific mRNA markers. A third approach involves the development of highly discriminatory quantitative methods for chromosome dosage analysis using digital polymerase chain reaction technology. It is likely that these and other methods yet to be developed would allow noninvasive prenatal diagnosis of chromosomal aneuploidies by maternal plasma nucleic acids to be realized in the near future.

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    ABSTRACT: Aim: To assess the accuracy of RHD and RHCE genotyping by real-time PCR, through the analysis of fetal DNA in plasma samples of Rh negative pregnant women. Methods: The study consisted in the collection of two tubes of blood (each with 3 ml) from 19 RhD negative pregnant women that attended the obstetric consultation at the Hospital Distrital of Figueira da Foz, E.P.E. One of the samples was used to perform blood typing and the other was used for fetal DNA extraction. The Rh genotype was determined by real-time PCR with specific primers and Taqman® probes for RHD, RHC, RHE, SRY and GLO genes. Results: In 88.2% of cases (15/17) the RHD genotype was concordant with the phenotyping data, with 1 false-positive result (5.9%) and a precision of 94% (pvalue=0.001; K=76.7%). For the RHC gene, there was concordance in 60% of cases (6/10), with 4 false-negative results (40%) and a precision of 60% (pvalue=0,175; K=31%). Relatively to the RHE gene, the concordance achieved was 100% (10/10), with a precision of also 100% (pvalue=0.002; K=100%). Conclusion: The present study confirms the precision of fetal RHD and RHE genotyping in maternal plasma. Performing a similar study with a superior number of samples could allow the implementation of this non-invasive prenatal diagnostic test in laboratorial and clinical routine, in order to follow pregnancies at risk for developing Hemolytic Disease of the Fetus and Newborn.
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    ABSTRACT: OBJECTIVES: Elevated albumin (ALB) mRNA concentration has been reported in the plasma of patients with liver diseases. The plasma ALB mRNA measurement was shown to be an effective indicator of liver pathologies with superior diagnostic sensitivity and specificity when compared with alanine transaminase (ALT). We hypothesized that serial plasma ALB mRNA analysis would be helpful in the early detection and monitoring of post-liver transplantation complications. DESIGN AND METHODS: One hundred and five blood specimens were collected from 24 post-transplant recipients. Biochemical liver function test profiles and plasma ALB mRNA concentrations were assessed. RESULTS: Over the study period, the health status of 14 recipients (58%) remained stable (Stable group). Their plasma ALB mRNA concentrations remained within a low-concentration range. In contrast, 10 recipients (42%) developed 14 episodes of hepatic complications (Unstable group). The median plasma ALB mRNA concentration of the Unstable group was 6.5-times higher than that of the Stable group. Plasma ALB mRNA concentration was elevated on 13/14 (93%) episodes of the hepatic complications while ALT was elevated only on 8/14 (57%) episodes. CONCLUSIONS: The elevation of plasma ALB mRNA may allow sensitive detection of hepatic complications and monitoring of the clinical course in a dynamic fashion. Serial plasma ALB mRNA measurement is potentially useful for post-liver transplantation management.
    Clinical biochemistry 04/2013; 46(15). DOI:10.1016/j.clinbiochem.2013.04.022 · 2.23 Impact Factor
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    ABSTRACT: The analysis of fetal nucleic acids in maternal blood 13 years ago has led to the initiation of noninvasive methods for the early determination of fetal gender, rhesus D status, and a number of aneuploid disorders and hemoglobinopathies. Subsequently, a comparatively large quantity of fetal DNA and RNA has been demonstrated in amniotic fluid as well as small amounts in premature infant saliva. The DNA and RNA in amniotic fluid has permitted an analysis of core transcriptomes, whilst the DNA and RNA in saliva allows the early detection and treatment monitoring of fetal developmental problems. These aspects are discussed together with the methodology and limits of analysis for noninvasive prenatal diagnosis in predictive, preventive, and personalized medicine.
    International Journal of Women's Health 04/2013; 5:177-86. DOI:10.2147/IJWH.S34442


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