Implementation of Exome Sequencing in Prenatal Diagnostics: Chances and Challenges

Abstract

Whole exome sequencing (WES) has become part of the postnatal diagnostic work-up of both pediatric and adult patients with a range of disorders. In the last years, WES is slowly being implemented in the prenatal setting as well, although some hurdles remain, such as quantity and quality of input material, minimizing turn-around times, and ensuring consistent interpretation and reporting of variants. We present the results of 1 year of prenatal WES in a single genetic center. Twenty-eight fetus-parent trios were analyzed, of which seven (25%) showed a pathogenic or likely pathogenic variant that explained the fetal phenotype. Autosomal recessive (4), de novo (2) and dominantly inherited (1) mutations were detected. Prenatal rapid WES allows for a timely decision-making in the current pregnancy, adequate counseling with the possibility of preimplantation or prenatal genetic testing in future pregnancies and screening of the extended family. With a diagnostic yield in selected cases of 25% and a turn-around time under 4 weeks, rapid WES shows promise for becoming part of pregnancy care in fetuses with ultrasound anomalies in whom chromosomal microarray did not uncover the cause.