Recent developments in the detection of fetal single gene differences in maternal plasma and the role of size fractionation.

The presence of cell-free fetal DNA in maternal plasma allowed noninvasive prenatal diagnosis of fetal loci completely absent from the maternal genome, such as SRY gene and RhD gene. However, the detection of fetal point mutations is hindered by the predominance of maternal DNA sequences. Recent studies have shown that cell-free fetal DNA exists in maternal plasma in small fragments. Thus, cell-free fetal DNA can be enriched by size fractionation, which improves detection of fetal gene mutations. Furthermore, it has been shown that Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry also permits the detection of fetal SNPs from maternal plasma. These two new developments are discussed.