Integrated Prenatal Genetic Evaluation of Renal Agenesis: Chromosomal Microarray Analysis, Whole Exome Sequencing,
Na Zhang1,2, Ruibin Huang2, Fang Fu2
1The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510620, China.
Objectives:
To characterize the prenatal phenotypic spectrum, genetic findings, and pregnancy outcomes of fetal renal agenesis (RA), and to clarify the complementary roles of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in phenotype-stratified prenatal evaluation.
Methods:
This retrospective study included 203 RA fetuses between March 2017 and November 2025. All cases underwent genome-wide copy number variant (CNV) analysis, and selected cases underwent WES. Detection rates were compared across subgroups by laterality, isolated vs. non-isolated phenotype, fetal sex, and presence of extrarenal anomalies. Pregnancy outcomes and postnatal imaging follow-up were collected when available. A systematic literature review of prenatal genetic testing in RA fetuses was performed.
Results:
Among 203 fetuses, unilateral RA accounted for 92.6% of cases, and 65.0% were isolated. Chromosomal abnormalities were identified in 15 fetuses (7.4%), including aneuploidies and pathogenic or likely pathogenic (P/LP) CNVs. WES identified P/LP single nucleotide variants in 8 of 127 cases (6.3%), increasing to 8.7% when variants with potential clinical relevance were included. Diagnostic yield of WES was significantly higher in bilateral RA, non-isolated cases, and fetuses with extrarenal anomalies. Postnatal follow-up confirmed RA in most liveborn cases, although additional phenotypes emerged in some children. Literature synthesis identified recurrent CNVs at 16p11.2 and 22q11.21 and frequent involvement of FRAS1, FREM2, GFRA1, and GREB1L.
Conclusions:
RA shows marked phenotypic and genetic heterogeneity. CMA remains a first-tier prenatal test, while WES provides substantial incremental yield in bilateral, non-isolated, or extrarenal-associated RA. Integrated, phenotype-driven testing with longitudinal follow-up supports improved prognostication and genetic counseling.
