Detection of Paternally Inherited Fetal Point Mutations for β-Thalassemia Using Size-Fractionated Cell-Free DNA in Maternal Plasma

Abstract
Monogenic disorders frequently involve point mutations. This single nucleotide exchange makes the analysis of point mutations more complex as stringent assays need to be established that permit a clear distinction between normal and mutant alleles. The prenatal diagnosis of this multitude of hereditary genetic disorders currently relies on invasive procedures,1 such as amniocentesis or chorionic villous sampling, which are associated with a small but significant risk of fetal loss.2,3 To avoid this procedure-related risk, several strategies have been considered for noninvasive assessment of fetal genetic traits, including the isolation of rare fetal cells from the maternal circulation and the analysis of circulatory fetal DNA in maternal plasma.1,4-6