Introduction: In pregnancy, the discovery of fetal DNA in maternal blood outlined new scenarios for noninvasive prenatal diagnosis of numerous fetal pathological conditions based on a new source of fetal genetic material. Tests on fetal DNA circulating in maternal plasma are expected to replace or reduce invasive procedures, such as chorionic villi sampling and amniocentesis, that are typically carried out late in pregnancy and pose a risk of miscarriage.
Areas covered: Nevertheless, at present, no accurate and simple methods for noninvasive prenatal diagnosis of genetic diseases are available, thus preventing a widespread clinical application.
Expert opinion: Two highly different sensitive methodologies are reported both allowing the identification of fetal paternally inherited mutations in maternal plasma DNA during the first trimester of pregnancy in a clinically relevant genetic disease. The first one includes mutant enrichment amplification protocols either based on the use of PNA (peptide nucleic acids) or on CO-amplification at Lower Denaturation temperature-PCR (COLD-PCR). In the second approach, an extremely sensitive microarray substrates are exploited which allows the detection of fetal mutated alleles even without the need of any enrichment strategy. Beta-thalassemia has been chosen as a model of clinically relevant genetic disease.