Non‐invasive prenatal testing of monogenic fetal characteristics by maternal plasma DNA analysis

Abstract

Since its discovery in 1997, cell‐free fetal DNA in maternal plasma has offered exciting avenues for non‐invasive prenatal testing of many fetal disorders, including monogenic diseases. Fetal sexing for sex‐linked diseases and congenital adrenal hyperplasia and Rhesus D genotyping are now clinically performed in many centres. Paternally inherited traits can be detected in maternal plasma to diagnose paternally inherited autosomal dominant disorders, while the absence of paternally inherited mutations can exclude autosomal recessive disorders. The precise quantification offered by single‐molecule counting technologies has facilitated the accurate measurement of genotype and haplotype imbalances in maternal plasma. Such measurements are useful for deducing the inheritance status of the foetus using approaches called relative mutation dosage analysis and relative haplotype dosage analysis. It has also been demonstrated that the entire fetal genome could be sequenced from maternal plasma. Feasibility studies have been performed for detection of fetal de novo mutations from maternal plasma. It is likely that the application of non‐invasive prenatal testing of maternal plasma for fetal monogenic diseases would increase in the near future.