Clinical utility of whole exome sequencing in the prenatal diagnosis with fetuses at risk

Abstract

Purpose: To investigate the clinical utility of whole exome sequencing (WES) in the prenatal diagnosis with fetuses at risk and variation information identified by WES. Methods: WES was conducted for 40 families with clinical informed consent, and the overall diagnosis rate and performance in different subgroups were analyzed. Genetic variants identified by ES were assessed according to the Mendelian model of inheritance. Results: Of the 40 prenatal specimens, there were 28 cases of amniotic fluid, 6 cases of villi and 6 cases of fetal tissues. And the average gestational age was 19.5±4.8 weeks. It revealed that a total of 8 pathogenic / likely pathogenic variants were detected which likely to be associated with the observed fetal anomalies, and the diagnosis rate was 20% (8/40). Among them, the detection rate of fetal ultrasound abnormal group could be up to 60% (6/10). All 8 diagnosed cases had inherited the relevant variants (5 variants were autosomal recessively inherited and 3 were dominantly inherited disorders). Conclusion: The application of whole exome sequencing to prenatal diagnosis can improve the clinical diagnosis rate. WES has the potential to improve the clinical management of pregnancies and provide risk of recurrence in future pregnancies. However, further investigation was needed to maximize clinical usefulness of prenatal WES in the future.