Objective: To explore the genetic etiology of fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) by whole exome sequencing (WES).
Methods: WES was performed on DNA extracted from cord blood samples of 26 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 19 cases, sequencing was performed on fetal DNA only, and the turnaround time was 11-12 weeks. For the remaining 7 cases, the fetus and its parents were sequenced simultaneously, and the turnaround time was 8-9 weeks.
Results: Of the 26 cases, pathogenic variants were identified in 4 (15.4%) cases, which respectively involved UMOD, NEK8, HNF1B, and BBS2 genes, and likely pathogenic variants were identified in 2 (7.7%) cases, which respectively involved HSPD1 and GRIN2B genes. Two of the 4 cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/19 (10.5%) for isolated CAKUT and 4/7 (57.1%) for CAKUT with additional anomalies.
Conclusion: The application of WES as a prenatal diagnostic approach for CAKUT fetuses with or without other anomalies allowed early and accurate diagnosis and improved their clinical management.