We have made evident the possibility of detecting an inherited paternal mutation in a non-invasive way at the 13t(hr) weeks of pregnancy. This methodology could be very useful in cases of paternally inherited dominant disorders. The technical improvements in fetal DNA detection and analysis might lead to the development of new applications in the non-invasive prenatal diagnosis field.

The discovery of fetal DNA in maternal plasma from early pregnancies has led to new opportunities for clinical application. In the last few years there have been numerous reported applications, mainly fetal gender and RhD genotyping. The prenatal diagnosis of some inherited genetic diseases such as Huntington disease is also very frequently required in the prenatal diagnosis routine. We have successfully diagnosed, with a non-invasive procedure, an unaffected HD fetus at the 13th week of gestation using fetal DNA from maternal plasma and the quantitative fluorescent PCR method, which is one of the most sensitive ways to detect fetal DNA in maternal plasma at such an early time of gestation.

The existence of foetal DNA in maternal blood, discovered in 1997, opened new possibilities for noninvasive prenatal diagnosis. This includes foetal sex assessment by the detection of specific Y chromosome sequences in maternal blood, particularly important when a foetus may be affected by an X-linked disorder such as haemophilia. This study aims to validate this sex assessment method and to test its clinical utility in the diagnosis of 15 potentially affected pregnancies in female carriers of haemophilia. In the validation study, 316 maternal blood samples from 196 pregnant women at gestations ranging from 5 weeks to 12 weeks were analysed. In the clinical study, 15 pregnancies at risk of having a haemophilic foetus were tested. All pregnancies in the validation study were correctly diagnosed. The accuracy and specificity of the methodology from the seventh week of gestation was 100%. The sex of all 15 pregnancies identified as being at risk of bearing a haemophilic foetus was correctly diagnosed. Foetal sex assessment by detecting specific Y chromosome sequences in maternal blood is now routinely used in our hospital because of its high accuracy from the seventh week of gestation. Reliable foetal gender determination from maternal blood of pregnant women carriers of haemophilia in the first trimester of gestation can avoid more conventional, invasive methods of prenatal diagnosis.

QF-PCR represents a useful and reliable tool to diagnose aneuploidies in spontaneous miscarriages. It provides information about parental and meiotic origin of anomaly, allowing an appropriate genetic counselling.