Updated: Jul 24, 2019
A non-invasive prenatal test to diagnose a risk of sickle cell disease in a baby is possible and may be available in clinics in a near future, if further testing confirms its efficacy, researchers in the U.K. report.
Julia van Campen presented the first results of the non-invasive test in the presentation “Non-invasive prenatal diagnosis of sickle cell disease by next generation sequencing of cell-free DNA” at the recent 2019 European Human Genetics Conference in Gothenburg, Sweden.
Sickle cell disease (SCD) is an autosomal recessive disease, meaning that a child has to inherit two mutated copies of the hemoglobin gene to develop it — one from each parent. If both parents have sickle cell trait, there is a 25 percent chance the child will have SCD.
Without early diagnosis and treatment, the life expectancy of children with SCD is only a few years.
Currently, sickle cell can only be diagnosed during pregnancy using an invasive test like amniocentesis that carries a risk, although small, of miscarriage, leading some parents to decline it. An earlier survey showed that if patients had the option of a non-invasive test, more would choose screening for the possibility of SCD.
“However, many couples are unaware that they are at risk until pregnancy occurs, even though carrier testing and follow-up genetic counseling is available through the UK National Health Service for those who are concerned that they may carry SCD,” Julia van Campen, a researcher at Guy’s and St Thomas, said in a press release. “It is important to raise awareness of SCD, which currently is limited.”
Researchers at Guy’s and St Thomas’ NHS Foundation Trust and Viapath Analytics, London, developed a non-invasive prenatal screening test that analyses the fetal DNA that circulates freely in the mother’s blood to determine the risk of her baby having SCD.
The test was developed in collaboration with the healthcare company Nonacus Ltd. in Birmingham.
“Although cell-free fetal DNA testing is already available for some disorders, technical difficulties have hampered the development of such a test for SCD, despite it being one of the most commonly requested prenatal tests in the UK, ” van Campen said.
Researchers analyzed blood samples from 24 pregnant carrying a mutated copy of the hemoglobin gene, and as such were sickle cell carriers. The scientists optimized their method to enrich the samples for the fetal DNA, and used a molecular barcode to identify the mutant and normal gene.
They successfully diagnosed SCD in 21 out of the 24 pregnancies using blood samples retrieved as early as eight weeks’ gestation. In the other three samples, results were inconclusive. The test is undergoing further research to confirm its diagnostics potential before it might be brought into clinical practice. For regular use, the test needs to be not only reliable, but also fast and affordable.
“I am excited that this work has given better results than I had expected, and am hopeful that people will be able to build on this work to make this test available in the near future,” said van Campen. “The development of non-invasive genetic tests that can be safely used during pregnancy is important to identify fetuses with severe disorders,” said professor Joris Veltman, director of the Institute of Genetic Medicine at Newcastle University and chair of the ESHG conference.
“These scientists have developed a novel state-of-the art genomics approach to do this for sickle cell disease in couples at risk. Their first results … indicate that their test is very promising,” Veltman added. This approach might also aid in diagnosing similar disorders in a fetus. “We demonstrate that NIPD [non-invasive prenatal test] for sickle cell disease is approaching clinical utility. Other autosomal recessive disorders may benefit from a similar approach,” the study concluded.