Non-invasive prenatal diagnosis of single gene disorders: How close are we?

SummaryAnalysis of cell free fetal DNA (cffDNA) in maternal plasma provides the opportunity for reliable, timely, safe and cost-effective diagnosis of single gene disorders. The detection of certain fetal loci using cffDNA and conventional molecular analytic approaches is possible from 4 weeks gestation. To date, non-invasive first-trimester analysis for single gene disorders has been limited by assay sensitivity and specificity, due to the background maternal DNA. The anticipated ability to enrich the fetal component of cell free DNA will increase the robustness of tests and permit semi-quantitative analysis, broadening the scope of testing to include recessive disorders such as cystic fibrosis. Testing for large-scale mutations might remain limited by the fragmented nature of cffDNA and, when testing very early in gestation, careful ultrasound examination will be needed to determine the number of gestational sacs, because of the risk of discordant twin pregnancies.