Down syndrome test

A drop of mother’s blood could soon be all it takes to tell whether an unborn baby has Down syndrome. This should reduce, and possibly eliminate, the need for invasive tests that can cause miscarriage.Currently, women deemed at high risk of giving birth to a child with Down syndrome — and who do not wish to do so — face the tough decision of whether to have an invasive test such chorionic villus sampling (CVS) or amniocentesis. The tests allow women to abort if they don’t want a child with Down, but they carry at least a 1 percent risk of miscarriage.
“I can’t tell you how much parents struggle with that decision,” says Jane Fisher of the UK charity Antenatal Results and Choices in London.A child with Down syndrome inherits an extra copy of chromosome 21 from either their mother or father. Now two research teams have devised blood tests — that carry no risk of miscarriage — to detect this extra copy by analyzing fetal genetic material shed into the mother’s blood.Though the findings are still preliminary, Dennis Lo of the Chinese University of Hong Kong, who first proposed fetal DNA testing in 1997, is optimistic that far fewer women will need invasive tests for Down. “This problem really appears to be solvable,” he says.Lo’s method, developed in 2007 (Nature Medicine), is now being commercialized by the company Sequenom of San Diego, Calif. The approach focuses on a stretch of chromosome 21 that is only expressed in fetuses. Sequenom looks for the RNA strand that is complementary to this stretch and determines which parent it comes from by identifying single-letter differences in the sequence called single nucleotide polymorphisms (SNPs).If the amount of chromosome 21 from each parent is roughly the same, the fetus is healthy; but if the quantity from one parent is about double that from the other, the fetus likely has Down syndrome. So far, the company has tested the method in 400 women, of which just 13 turned out to have fetuses with Down. However, the RNA test picked up every case and did not flag any “false positives”.One disadvantage of Sequenom’s technology, though, is that SNPs vary between populations, so the test may not work outside the United States. “This is not ready for use in the UK,” says Lyn Chitty, who studies fetal medicine at University College London.Enter Stephen Quake and colleagues at Stanford University in California. In early October, they reported results from a technique that doesn’t depend on SNPs. “Our approach works on 100 percent of the population, independent of ethnicity,” Quake says.The researchers use “shotgun sequencing” on short fetal DNA fragments in the mother’s blood. They then trace each fragment to the chromosome it came from and calculate the proportion from chromosome 21.The team tested the technique using blood samples from 18 pregnant women — half with healthy fetuses and half carrying fetuses with Down syndrome. They found that in the women with Down fetuses, the proportion of chromosome 21 fragments was 11 percent higher on average (Proceedings of the National Academy of Sciences).Both groups believe their tests have great potential. Sequenom plans to start offering the RNA test to U. S. doctors in mid-2009 after further studies. Though the test won’t replace invasive methods initially, it should vastly reduce the number of women who need to consider it, says Betty Dragon of Sequenom.“You are putting fewer children at risk for the invasive procedure,” she says. Quake meanwhile believes the shotgun sequencing approach will make invasive testing obsolete.Though Chitty thinks both methods are exciting, she cautions against raising pregnant women’s hopes just yet. For one thing, the techniques need to be tested on much larger numbers of people. Also, Quake’s team drew blood samples after the women had undergone CVS or amniocentesis, and some researchers say such invasive tests may trigger the release of fetal DNA, pushing the accuracy of the blood test above what it would be on its own. Quake’s team disputes this. They say the proportion of fetal to maternal DNA found in their study (about 10 percent) falls within the normal range.At the very least, the tests seem likely to be a good way of flagging up women at high risk of having a baby with Down syndrome — and so reducing the number who need CVS or amniocentesis. Whether they could be used as the sole means of diagnosis remains to be seen, says Diana Bianchi, professor of pediatrics, obstetrics and gynecology at Tufts University School of Medicine, Boston, Mass.