ArticleHuman genetics2012
Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations.
Article in Human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 90 citations in OpenAlex.
- Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling.bioRxiv : the preprint server for biology · 2026Article
- Dose-Dependent and Non-Autonomous Signaling in CAKUT: A Lineage-Specific Framework from Conditional Knockout Studies.Biomolecules · 2026Review
- Etiology and outcomes of fetal renal abnormalities in Southern China: a single-tertiary-center study.Orphanet journal of rare diseases · 2025Article
- Translational strategies to uncover the etiology of congenital anomalies of the kidney and urinary tract.Pediatric nephrology (Berlin, Germany) · 2025Review
- Harnessing mechanobiology for kidney organoid research.Frontiers in cell and developmental biology · 2023Review
- Regulation of nephron progenitor cell lifespan and nephron endowment.Nature reviews. Nephrology · 2022Review
- Disease mechanisms of monogenic congenital anomalies of the kidney and urinary tract American Journal of Medical Genetics Part C.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Single-Cell Gene Expression Analysis in Patients with Medullary Sponge Kidney and a Retrospective Study.BioMed research international · 2022Article
- RET receptor signaling: Function in development, metabolic disease, and cancer.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Decade in review: a new era for RET-rearranged lung cancers.Translational lung cancer research · 2020Review
- Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice.Scientific reports · 2020Article
- Article
- DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Unique association of multiple endocrine neoplasia 2A and congenital anomalies of the kidney and urinary tract in a child with aBMJ case reports · 2019Article
- SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes.Kidney international · 2019Article
- Development of the urogenital system is regulated via the 3'UTR of GDNF.Scientific reports · 2019Article
- Broad Phenotypes of Disorders/Differences of Sex Development inFrontiers in genetics · 2019Article
- Medullary Sponge Kidney: Current Perspectives.International journal of nephrology and renovascular disease · 2019Article
- Could the interaction between LMX1B and PAX2 influence the severity of renal symptoms?European journal of human genetics : EJHG · 2018Article
- Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Signaling by the glial cell line-derived neurotrophic factor (GDNF)-RET receptor tyrosine kinase and SPRY1, a RET repressor, is essential for early urinary tract development. Individual or a combination of GDNF, RET and SPRY1 mutant alleles in mice cause renal malformations reminiscent of congenital anomalies of the kidney or urinary tract (CAKUT) in humans and distinct from renal agenesis phenotype in complete GDNF or RET-null mice. We sequenced GDNF, SPRY1 and RET in 122 unrelated living CAKUT patients to discover deleterious mutations that cause CAKUT. Novel or rare deleterious mutations in GDNF or RET were found in six unrelated patients. A family with duplicated collecting system had a novel mutation, RET-R831Q, which showed markedly decreased GDNF-dependent MAPK activity. Two patients with RET-G691S polymorphism harbored additional rare non-synonymous variants GDNF-R93W and RET-R982C. The patient with double RET-G691S/R982C genotype had multiple defects including renal dysplasia, megaureters and cryptorchidism. Presence of both mutations was necessary to affect RET activity. Targeted whole-exome and next-generation sequencing revealed a novel deleterious mutation G443D in GFRα1, the co-receptor for RET, in this patient. Pedigree analysis indicated that the GFRα1 mutation was inherited from the unaffected mother and the RET mutations from the unaffected father. Our studies indicate that 5% of living CAKUT patients harbor deleterious rare variants or novel mutations in GDNF-GFRα1-RET pathway. We provide evidence for the coexistence of deleterious rare and common variants in genes in the same pathway as a cause of CAKUT and discovered novel phenotypes associated with the RET pathway.
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