Abstract
<title>Abstract</title> <p> Background Renal agenesis (RA) is a rare congenital fetal malformation associated with an increased risk of perinatal death, childhood renal dysfunction, and end-stage renal disease. In total, 25,000 pregnant women who received a prenatal diagnosis between January 2016 and February 2026 were enrolled in this retrospective analysis. Prenatal ultrasound identified 87 fetuses with RA. Amniotic fluid and umbilical cord blood samples were collected at different gestational ages for chromosomal karyotyping and chromosomal microarray analysis (CMA). Whole-exome sequencing (WES) was performed in selected cases. Chromosome karyotype analysis was performed on 85 fetal samples. Result Except for one case of amniotic fluid cell culture failure in a pregnant woman with advanced gestational age, only two cases of fetal chromosomal aneuploidy were found. Along with 2 cases consistent with karyotype results, 11 additional cases of Copy Number Variations (CNVs) were detected. Among these, 9 cases were pathogenic CNVs and 2 had unknown clinical significance. Further, 9 RA fetuses with negative karyotype and CMA underwent further WES, and two single gene mutations were detected in <italic>BCOR</italic> and <italic>ANOS1</italic> , respectively. In total, 84 fetuses with RA were successfully followed up, of which 20 underwent termination of pregnancy (8 with pathogenic CNVs and 2 with single gene mutations), 3 pregnant women were still pregnant, and 61 were live births. Postnatal follow-up of the 61 live births revealed associated anomalies in 7 infants (including one postnatal death due to cardiac disease), whereas the majority (n = 54) had a favorable outcome. Conclusion RA is correlated with copy number variations and single gene mutations, and the detection rate of genetic abnormalities is significantly increased when combined with ultrasound soft markers and other structural malformations. Follow-up showed that the pregnancy outcome of RA fetuses mainly depended on the presence of pathogenic genetic abnormalities and severe structural abnormalities. Fetuses with bilateral renal agenesis underwent termination of pregnancy, whereas most fetuses with unilateral renal agenesis were born alive and grew well. These findings may provide evidence for prenatal genetic counseling, precise diagnosis, and perinatal management of affected fetuses </p>