Noninvasive prenatal diagnosis of early onset primary dystonia I in maternal plasma.

OBJECTIVE: The genetic trait of a fetus may be determined early on in pregnancy using cell-free fetal DNA extracted from the plasma of pregnant women. The challenges for noninvasive diagnosis include the variable but still low amount of cell-free fetal DNA in the first trimester (57-761 gE/mL) and the competing high background of maternal DNA in the plasma ( approximately 90%). Prenatal detection of a paternally inherited dystonia 3 bp deletion mutation was undertaken using cell-free DNA (cfDNA) from the plasma of two at-risk pregnancies. The predicted fetal genotype was subsequently confirmed in each fetus.

METHOD: Cell-free fetal DNA was extracted from the plasma of two pregnancies between 8 and 9 weeks' gestation as determined by fetal ultrasound scan. Analysis was by PCR amplification with size separation using polyacrylamide gel electrophoresis and detection by ethidium bromide staining.

RESULTS: In both pregnancies the c.904_906delGAG DYT1 mutation was detected in the maternal plasma and then confirmed in the subsequent fetal tissue verifying that the fetus had inherited the paternal mutation.

CONCLUSION: The detection of a paternally inherited DYT1 mutation in maternal plasma was undertaken using simple, rapid, and inexpensive techniques with minimal risk of contamination. Further developments in the enrichment for fetal cfDNA will enhance the detection of point mutations in monogenic disorders.