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Noninvasive prenatal test shows potential for sickle cell disease diagnosis
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A noninvasive prenatal test developed by researchers in the United Kingdom appeared effective for diagnosis of sickle cell disease among a small patient sample.
“We have developed a method for testing for sickle cell disease using cell-free fetal DNA — DNA from the fetus that circulates in the maternal bloodstream,” Julia van Campen, PhD, research scientist in the department of genetics at Guy’s Hospital in London, said in a press release.
Sickle cell disease currently is diagnosed during pregnancy through an invasive test that carries a small risk for miscarriage, according to the release. Previous attempts to develop a noninvasive prenatal assay have been unsuccessful.
For this reason, van Campen and colleagues sought to assess the efficacy of a novel noninvasive test for prenatal diagnosis of sickle cell disease.
They used targeted next-generation sequencing of cell-free DNA pooled from 24 maternal plasma samples and incorporated unique molecular identifiers into library preparation for accurate quantification of mutant and wild-type allele reads.
Of the 24 plasma samples, 21 were concordant with the established genotype, and researchers successfully genotyped samples from as early as 8 weeks gestation.
HemOnc Today spoke with van Campen about the assay and when it may become available in practice.
Question: Why is a test like this needed?
Answer: Noninvasive prenatal diagnosis provides increased choice to women whose pregnancy is at risk for a genetic disorder. Although noninvasive prenatal diagnosis is already available for some disorders, technical difficulties have hampered development of such a test for sickle cell disease — despite it being one of the most commonly requested prenatal tests in the United Kingdom.
Q: Why might a test like this work for this specific patient population?
A: Previous research has shown that if the option of a noninvasive test were available, more women whose fetuses are at risk for sickle cell disease would opt for prenatal testing. The development of a noninvasive prenatal assay for sickle cell disease has been attempted before and, until now, has not been successful.
Q: Can you briefly describe how the test works?
A: We performed sequencing of cell-free DNA from maternal plasma and counted the sequencing reads representing the mutant or normal ‘wild-type’ beta-hemoglobin gene. Using unique molecular identifiers, a type of molecular barcode, we were able to reduce errors, and by analyzing only smaller fragments, we enhanced the fetal contribution to the samples. In this way, we could accurately determine the dosage of the mutant and normal sequencing reads, which we then used to determine fetal sickle cell disease status.
Q: What type of efficacy have you and your colleagues observed so far?
A: We achieved successful diagnosis of sickle cell disease status for 21 out of 24 pregnancies tested so far in samples from as early as 8 weeks gestation. Three samples provided inconclusive results.
Q: When will we see the test used in practice for this patient population?
A: Before the assay can be introduced in clinical practice, it needs to be tested on more samples. We also need to ensure that it can provide results rapidly enough to give women answers at the right time during their pregnancy, and that it can be performed at a cost that health care providers can afford. – by Jennifer Southall
Reference:
Van Campen JC, et al. Abstract C08.5. Presented at: European Human Genetics Conference; June 15-18, 2019; Gothenburg, Sweden.
For more information:
Julia van Campen, PhD, can be reached at Guy’s Hospital, 5th Floor Tower Wing, London, UK, SE1 9RT; email: Julia.VanCampen@gstt.nhs.uk.
Disclosure: The study was funded by the Guy’s and St. Thomas’ Hospital Charity. van Campen reports no relevant financial disclosures.