GREB1L and Bilateral Renal Agenesis

Bilateral renal agenesis (MONDO:0015986) represents the most severe form of the congenital anomalies of the kidneys and urinary tract (CAKUT) spectrum. In two unrelated families, recurrent pregnancies affected by bilateral renal agenesis were found to harbor likely pathogenic variants in the GREB1L gene, inherited from asymptomatic fathers—one of whom exhibited a unilateral pelvic kidney on ultrasound—demonstrating autosomal dominant transmission with reduced penetrance and confirming GREB1L as a candidate gene for this phenotype (2 probands) ([PMID:40041231]).

Further support comes from a clinical exome sequencing study in a Chinese family with renal agenesis, which identified a novel missense variant, c.2333T>A (p.Val778Asp), absent in 100 controls and predicted to damage GREB1L protein function ([PMID:32598191]). Although no additional segregation beyond the index cases has been reported, these findings extend the variant spectrum and underscore the gene’s role in kidney development.

References

• Case reports in perinatal medicine • 2022 • Challenges in genetic counseling for congenital anomalies of the kidneys and urinary tract (CAKUT) spectrum. PMID:40041231
• Genetic testing and molecular biomarkers • 2020 • Clinical Exome Sequencing Identifies a Novel Mutation of the GREB1L Gene in a Chinese Family with Renal Agenesis. PMID:32598191

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