A New Era of Genomics for Fetal Diagnosis


NIH National Institute of Child Health and Human Development (NICHD)

Principal Investigator

Dr. Neeta Vora, Obstetrics and Gynecology

Project Run Dates

6/01/2017 to 6/30/2021



Whole exome sequencing (WES) is an innovative genomic technology that has proven to be a powerful diagnostic tool in adults and children but has not been studied for fetal genetic diagnosis. Standard prenatal fetal genetic testing with karyotype and microarray only provides a diagnosis in 10% of anomalous fetuses suspected to have a genetic syndrome, leaving the majority of families with uncertainty about diagnosis as well as recurrence risk in subsequent children. To evaluate the use of this transformative technology for evaluation of fetuses with multiple structural anomalies, I will apply WES in pregnancies complicated by a fetus with multiple congenital anomalies suspected to have a genetic etiology not identified by standard genetic testing. I will perform ES testing on 52 such maternal/paternal/fetal triads. The goal of aim 1 is to identify major genetic abnormalities associated with fetal death in fetuses suspected to have a genetic etiology not identified by standard genetic testing. We will use WES on fetal specimens (amniocytes, chorionic villi, or umbilical cord blood). By completing Aim 1, we will be able to evaluate the performance of WES in a prenatal population, and identify critical clinical characteristics that can guide its application. Aim 2 will measure the impact of fetal genetic information on parents. This information will be used to develop an ethical framework for the introduction of WES into a prenatal setting and a set of considerations to include in decision aids, counseling protocols, and quantitative surveys for use in future studies of prenatal exome sequencing. The results from this proposal are the first step toward my long term goal to establish a set of best practices to guide future implementation of new and innovative genomic technologies in the prenatal setting to benefit families affected by fetal genetic disorders.


Associated Publications and other materials


Associated Award Numbers: A17-1507-001, 1-K23-HD088742-01A1