20 millilitres of blood to diagnose Down syndrome
Down syndrome, or trisomy 21, occurs when there is an extra copy of chromosome 21. LifeCodexx AG has developed PraenaTest®, an innovative diagnostic test that is able to reliably confirm or exclude trisomy 21 from a blood sample of a pregnant woman. The non-invasive test developed by the Konstanz-based biotech company has recently been placed on the market as an alternative to current invasive tests which result in up to 700 miscarriages per year in Germany alone.
Down syndrome, also known as trisomy 21, is a chromosomal condition caused by the presence of a third copy of chromosome 21 instead of the usual two in each cell in the body. Current tests to confirm or exclude trisomy 21 involve invasive methods, including chorionic villus sampling from the placenta, or amniocentesis. Both methods provide reliable results; amniocentesis has a reliability rate of up to 99.9 percent.
Despite the reliability of the tests, they nevertheless represent a risk for the unborn babies. The risk of miscarriage from amniocentesis and chorionic villus sampling is around 0.2 to 1 percent. The innovative PraenaTest® offers the possibility of significantly reducing the number of miscarriages resulting from amniocentesis and chorionic villus sampling. “The new method could potentially save the lives of up to 700 children in Germany alone,” Elke Decker, Director Strategic Marketing & Corporate Communications at LifeCodexx AG, said.
Cell-free DNA is used for testin
The innovative test is based on the analysis of cell-free DNA (cfDNA) (1) in the blood of pregnant women. cfDNA is not enclosed by cells, is present in small fragments and circulates freely in the blood of pregnant woman. “Besides maternal DNA, the blood of pregnant woman contains between two and 30 percent (on average around 10 percent) foetal DNA (cell-free foetal DNA, cffDNA),” Elke Decker explained. This DNA is derived from dead placental cells that are released into the women’s blood (2). The individual fragments have a lifespan of under two hours; cffDNA can thus no longer be detected in the blood of a baby’s mother even just a few hours after birth (3).
The non-invasive PraenaTest® is based on molecular biology and bioinformatic methods and designed to examine whether there is an elevated amount of chromosome 21-related cffDNA and hence confirm or exclude the presence of trisomy 21 (Down syndrome) in the unborn baby. The examination only requires 20 ml of venous blood from the pregnant woman.
Test involves next-generation sequencing
The test is based on innovative high-throughput sequencing methods (next-generation sequencing) applied to the DNA isolated from the blood plasma of pregnant women. These methods enable millions of DNA fragments to be sequenced in one single run. The sequences are pre-screened according to defined quality criteria. “A specifically developed software programme subsequently compares the sequence fragments with the individual chromosomes of the human genome and determines the quantity of chromosome 21 DNA,” Elke Decker explained (see figure). A validated algorithm then calculates whether the quantity of chromosome 21 DNA detected is within the standard range or not.
Reliability of the test has been clinically tested
PraenaTest® is only available to pregnant women in the 12th week of pregnancy or later who have a higher risk of chromosomal alterations in the unborn child. The result of the examination is available two to three weeks after blood has been taken from the pregnant women. The efficiency in diagnosing trisomy 21 in the blood of pregnant women was examined in clinical studies and rated as relatively high. Five prenatal centres and university hospitals in Germany and Switzerland collected blood samples of more than 500 pregnant women who had a higher risk of chromosomal alterations in the unborn child.
On average, the PraenaTest® detected the chromosomal alteration with a sensitivity of at least 95 percent and a false-positive rate of up to 0.5 percent. The blood test is now available in more than 70 qualified prenatal diagnostics practices and hospitals in Germany, Austria, Liechtenstein and Switzerland,” Elke Decker explained.
In the pipeline: tests for diagnosing trisomy 13 and 18
The company is now using the newly developed DNA-based prenatal test to develop tests to address other chromosomal alternations in unborn babies. “We will be able to use PraenaTest® for the diagnosis of trisomy 13 and 18 in the foreseeable future,” said Decker. Trisomy 13, also known as Patau syndrome, results from a genome mutation and is characterised by a third copy of chromosome 13. Children with Patau syndrome suffer from severe mental deficiency. Trisomy 18, also known as Edwards syndrome, is a severe developmental disorder that is caused by the presence of all or part of an extra 18th chromosome.
Elke Decker MSc. MBA
Director Strategic Marketing, Communication & Business Administration
(1) Lo et al., Lancet 1997;350:485-487
(2) Bischoff et al., Human Reproduction Update 2004;11:59-67
(3) Lo et al., Am J Hum Genet 1999;64:218-224