A blood test to enable non-Invasive Prenatal Diagnosis for Monogenic Diseases: MG-NIPD

Hubrecht Institute together with biotech company Cergentis collaborated to develop and validate a generic method for non-invasive prenatal diagnosis. Offering such method in the clinic is much desired, as currently parents with a severe monogenic disease (e.g cystic fibrosis, sickle cell disease. Duchenne dystrophy) who are opting for prenatal diagnosis rely on burdensome invasive diagnostic methods. MG-NIPD as they previously published provided academic proof-of-concept, but was too impractical for clinical implementation. Here, they proposed to transform MG-NIPD into a generic all-in-one method suitable for diverse monogenic diseases and compatible with routine diagnostic requirements. MG-NIPD requires targeted haplotyping of the disease gene, which implies assigning many tens to hundreds of neutral genetic variants specifically to the disease or the non-disease gene locus. This genetic information subsequently enables to unambiguously identify in cell-free (cf)DNA from the pregnant mother which allele each parent has transmitted to the fetus, and thus to determine its disease-status.

For haplotyping, Cergentis’ proprietary method for targeted gene analysis was used and further optimized. MG-NIPD yields complex genetic datasets, for which analytical software tools were developed. Optimized MG-NIPD was applied to blood samples of more than thirty couples who voluntarily and anonymously participated in an medical-ethically approved study. Results were compared to routine invasive prenatal diagnosis, which confirmed the promise of MG-NIPD as a simple blood test to replace surgery in future prenatal diagnosis. Further optimization of analytical tools is needed and ongoing to guarantee successful diagnosis of more pregnancies and diseases, and further validation is needed to implement MG-NIPD in routine clinical diagnostics.