The Diagnostic Value of Whole Exome Sequencing in Prenatal Fetal Structural Anomalies: A Study Based on the North-Central Region of Guangxi

Objective: Prenatal fetal structural abnormalities are one of the serious birth defect disease groups that endanger the life and health of newborns. Whole exome sequencing (WES) has been widely applied in the diagnosis of pediatric genetic diseases in clinical practice. This study is based on a cohort study in the central and northern regions of Guangxi, aiming to evaluate the efficiency of WES in diagnosing prenatal fetal congenital structural abnormalities. Method: 160 pregnant women whose fetal structural abnormalities were found by ultrasound examination and whose results were negative by karyotype analysis and CNV-seq testing, were collected. Further WES testing was performed to identify the related pathogenic genes. The pregnancy outcomes of pregnant women were collected. Result: This cohort study included 160 couples. Through karyotype analysis and CNV-seq testing, 138 (86.25%, 138/160) cases without detected abnormalities, WES identified pathogenic or likely pathogenic variants (P/LP) in 35 (25.36%, 35/138) cases, variants of uncertain significance (VUS) in 4 (2.90%, 4/138) cases. In WES testing, the most frequently affected organs was the skeletal system (19.38%). Among them, FGFR3 was the most common pathogenic mutant gene, followed by ACE, ASPM, CHD3, etc. The turnaround time (TAT) of WES synchronized with conventional prenatal diagnostic techniques was 22.46 days, much shorter than the 39.02 days of traditional sequential testing. A total of 154 pregnancy outcome data of pregnant women were obtained, among which 81 cases terminated their pregnancies. Conclusion: WES plays an important role in prenatal diagnosis and fetal structural abnormality diagnosis. Conducting WES in parallel with conventional prenatal diagnosis technology can significantly reduce TAT of prenatal diagnosis, improve the efficiency of clinical prenatal diagnosis of abnormal fetus. At the same time, the newly discovered gene variants expand the expression spectrum of genetic diseases and enrich the prenatal diagnosis database in central and northern region of Guangxi.