Prenatal genetic diagnostics
NIPT – examination of foetal DNA from mother’s blood
Generally
PRENASCAN is a reliable non-invasive genetic test for revealing trisomy of chromosomes 21 (Down Syndrome), 18 (Edwards Syndrome) and 13 (Patau Syndrome), which are the most common chromosomal numerical deviations (aneuploidy); the majority originate randomly with conception. Chromosomes are blocks of genes of typical shape and number. A human has 23 pairs of chromosomes numbered according to their size; one of the pair comes from the mother and one from the father. The sex cells – eggs and sperm – have half the number of chromosomes, which are paired after conception. The most common reason for trisomy is erroneous development of the sex cell with extra chromosomes. This error most commonly affects the eggs and the risk of it occurring rises with the mother’s age. The high excess number of genes with trisomy leads to disorders of overall appearance, congenital defects of various organs and delayed mental development. At present there is no effective prevention or treatment of these diseases and the life prognosis of affected individuals is unfavourable.
In cooperation with the largest company in the area of genomics in the world – BGI we now offer new non-invasive prenatal genetic test that reveals the multiplication of chromosomes no. 21 (Down Syndrome), no. 18 (Edwards Syndrome), and no. 13 (Patau Syndrome) of the foetus directly from the mother’s blood without the necessity of an invasive examination (amniocentesis, CVS). For the examination the “scanning of a new generation” technique is used linked with bioinformational analysis of the results. This method is non-invasive, with high sensitivity without the risk of miscarriage or infection.
Comparison of selected NIPT
| Chromosomes | Aneuploidy of sex chromosomes | Microdeletion syndromes | Multiple pregnancy | IVF | Determining of foetal fraction | Results | Week of pregnancy | Price | |
|---|---|---|---|---|---|---|---|---|---|
| PRENASCAN | 21, 18, 13, X, Y, 16, 22 | Yes | Yes | Yes | Yes | Yes | to 7 days | From 10th | 440 € |
| Trisomy test | 21, 18, 13, Y | No | No | Yes, but it can obscure the result | Yes | Yes | to 5 to 8 days | From 11th | 350 € |
| Trisomy test + | 21, 18, 13, X, Y, 16, 22 | Yes | Yes | Yes, but it can obscure the result | Yes | Yes | to 5 to 8 days | From 11th | 500 € |
- 99.91% for trisomy no. 21 (Down Syndrome)
- 98.79% for trisomy no. 18 (Edwards Syndrome)
- 98.7% for trisomy no. 13 (Patau Syndrome)
- 95.0% for monosomy X (Turner Syndrome)
- trisomy of chromosomes: for no. 9, for no. 16 for no. 22
- microdeletion syndromes: 1p36, Van der Woude’s syndrome (1q32.2), 2q33.1, Cri-du-Chat (5p) so-called cat’s cry syndrome, DiGeorge syndrome II (10p14-p13), Jacobsen’s syndrome (11q23), Prader-Willi/Angelman syndrome (15q11.2), 16p12
With each NIPT testing and PRENASCAN, the risk, albeit a small one, of a false negative result remains. On the other hand, if a positive result is found it needs to be verified with an invasive chorionic villus sampling (CVS) or amniocentesis (AMC) examination. The results of this test may be distorted if the mother of the foetus herself has a chromosomal abnormality, if the test is performed at the time of pregnancy, when there is not yet sufficient free DNA of the foetus in the mother’s blood, in multiple pregnancies or if the foetus has a rare combination of chromosomal defects (e.g. chimerism, microduplication, microdeletions). The results of NIPT may also be distorted by foreign DNA, if the mother got a transfusion or is post-transplantation of stem cells.
A part of the processes of controlling the quality of PRENASCAN testing is the stating of the percentage of free foetal DNA (cffDNA) in the testing report. The effectiveness of the PRENASCAN with twins is similar as with a single pregnancy.
The test is done from the 10th week of pregnancy. A blood sample is taken from the pregnant woman and is subsequently sent to a laboratory. The test results are available within 7 days from delivery. The examination has to be repeated in perhaps 1-2% of samples.
How?
PRENASCAN is proposed as a contingency screening for pregnant women with an increased risk of trisomy of chromosome no. 21, 18 and 13, with an atypical results of screening with the borderline risk, at age over 35 years, and during assisted reproduction.
PRENASCAN is not recommended as the test of first choice with findings of structural aberrations of the foetus determined by ultrasound and with a positive multiple marker combined test with risk for chromosomal aberration of more than 1:10. In these cases we recommend examinations of the foetus by methods of invasive prenatal diagnostics – chorionic villus sampling (CVS) or amniotic fluid (AMC).
The principle of a PRENASCAN is founded on examination of free foetal DNA, which circulates in the mother’s blood. Blood is made up of cells and plasma. Free circulating DNA fragments released from disintegrated cell nuclei can be shown in the plasma; in the plasma of a pregnant woman there is a mixture of DNA fragments of the mother of foetus. Using the method of massive parallel sequencing (MPS) it’s possible to assign each of millions of DNA fragments in the mother’s plasma to the chromosome from which it comes and to thus determine the excess of DNA of a certain chromosome, which is caused by trisomy of the foetus.
