Analysis of 26 fetuses with congenital anomalies of the kidney and urinary tract by whole exome sequencing

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. Key words: Whole-exome sequencing; Congenital anomalies of the kidney and urinary tract; Prenatal diagnosis; Monogenic disorder