To explore the application value of chromosome microarray analysis (CMA) combined with whole exome sequencing (WES) in the diagnosis of genetic etiology of fetuses with congenital anomalies of the kidney and urinary tract (CAKUT).

A total of 127 singleton pregnant women with CAKUT diagnosed by prenatal ultrasonography were selected from the Center of Prenatal Diagnosis of the First People′s Hospital of Huai′an, Nanjing Medical University from January 2008 to January 2021. Genetic analysis was conducted using CMA technique. Isolated CAKUT samples negative for CMA were analyzed by WES.

CMA was performed on 127 cases, identified 3 patients (2.36%) with chromosomal aneuploidy including 47, XXY, 47, XX, + 21 and 47, XX, + 18. Six patients carried pathogenic copy number variations (CNVs) and 2 patients carried likely pathogenic CNVs. The total detection rate of pathogenic and likely pathogenic CNVs was 6.30% (8/127). In 41 fetuses with CMA who were no abnormality, WES identified pathogenic variants in 3 patients (7.32%), and involved genes were PKD1, ACTA2 and PKHD1. In addition, incidental variations were detected in 2 cases, and the involved genes were INF2 and PPM1D.

CMA testing is recommended as a first-tier test for fetuses with CAKUT, and prenatal WES is a supplementary approach for the etiologic diagnosis of unexplained isolated CAKUT with negative CMA. The results show that a step-by-step and elimination approach could effectively improve the efficiency of prenatal CAKUT genetic testing.