Invasive prenatal testing for detection of chromosome abnormalities has been offered for more than 40 years, first by amniocentesis in the early 1970s and additionally by chorionic villus sampling in the early 1980s. The ability to isolate fetal cells and fetal DNA from maternal blood during pregnancy has opened up exciting opportunities for improved noninvasive prenatal testing (NIPT). There have now been numerous reports on the use of cell-free DNA (cfDNA) for NIPT of chromosomal aneuploidies starting from week 10 of pregnancy. The unmet needs were for monogenic disorder diagnosis and for earlier timing to noninvasive diagnosis.
In order to address the first challenge of noninvasive prenatal diagnosis (NIPD) for monogenic disorders, we tested 10 Gaucher disease carrier couples of Ashkenazi Jewish ethnicity. By applying highly targeted next generation sequencing (NGS) we were able to correctly identify all the pregnancies. Confirmation of the genetic status of the fetuses was performed after the children were born with 100% accuracy. This is one of the first attempts to noninvasively diagnose both maternal and paternal mutations for monogenic disorders during pregnancy. This research demonstrated that , fine-mapping of a founder mutation fingerprint is valuable asset for NIPD of autosomal recessive disease.
The second challenge was very early (week 5-6 of pregnancy) noninvasive pregnancy testing for monogenic disease. For this study we recruited cystic fibrosis carrier couples. We developed a new ultra-sensitive targeted next generation sequencing method for noninvasive haplotype-based paternal allele exclusion testing of the cystic fibrosis-associated gene, CFTR. This allowed us to detect paternal mutations from as early as five weeks of pregnancy most of the recruited families.
Noninvasive prenatal testing is emerging as an alternative to the conventional invasive prenatal testing methods of today. Its advantages include no risk of miscarriage and genetic diagnosis in very early stage pregnancy. Therefore the new test is an attractive choice for expectant couples who seek the most advanced and improved of prenatal diagnostic tools.