A would-be mom worried about Down syndrome faces an unpleasant choice: undergo an invasive test that can kill her fetus, or forgo a definitive answer until after birth. But a new method that involves tracing differences between a mother's DNA and her baby's could provide doctors with a safe and inexpensive way to diagnose the condition, one practical enough to become a part of routine prenatal care.
Down syndrome is the world's most common genetic condition, affecting about one in every 700 live births. Babies with the disorder carry an extra copy of chromosome 21, which causes cognitive disabilities, heart defects, and other problems. Although certain markers in a mother's blood can tip off doctors that a fetus is at higher risk of Down syndrome, only invasive and expensive procedures such as amniocentesis—which requires poking a needle into the uterus to obtain a fluid sample—can give a 99% accurate answer. But these invasive tests are risky: They can cause miscarriage in 1% to 2% of cases.
In an attempt to find a safer alternative, researchers have turned to the mother's blood. In a recent study, scientists ferreted out the fragments of fetal DNA that leak into a mother's bloodstream and then sequenced both genomes to check for extra copies of chromosome 21. Those attempts were successful, but they were time-consuming and required specialized and expensive DNA-sequencing equipment that would put the process out of reach for most people.
Philippos Patsalis wanted something more accessible. A geneticist at the Cyprus Institute of Neurology and Genetics in Nicosia, Patsalis has provided diagnostic prenatal testing for 20 years and has long lamented that women who want accurate testing face greater risk and expense.
The first step was finding a simpler way to isolate fetal DNA from the mother's bloodstream. Instead of sequencing entire genomes, as the previous researchers had done, Patsalis and colleagues focused on a process called DNA methylation. Here, chemical compounds called methyl groups attach to regions of DNA and, like a volume knob on a stereo, turn the activity of a gene up or down. Fetuses have methylation patterns that are different from their mothers', which allowed Patsalis's group to easily distinguish DNA from the two in the mother's blood.
Once the researchers had isolated fetal DNA, they began to look for signs of Down syndrome. They made several copies of the DNA and then looked for extra versions of chromosome 21. Here, too, methylation patterns simplified the process. Chromosome 21 has its own pattern of DNA methylation, which helped Patsalis's team find the extra copies more easily.
The approach worked. Among 80 women who were 11 to 14 weeks pregnant, the method was 100% accurate, using only standard equipment available in any basic diagnostic laboratory, says Patsalis. The results, published online today in Nature Medicine, "could blow away the current prenatal testing method," says geneticist Joris Vermeesch of the University of Leuven in Belgium, who was not involved in the study. "This is the Holy Grail of prenatal diagnosis."
Patsalis's team has plans for larger-scale clinical trials in the coming months. Their method's simplicity, low cost, and potential for spotting other genetic conditions makes them confident, Patsalis says, that the method "could be introduced in a clinical setting within 2 years."