ArticleHuman molecular genetics2017
A human patient-derived cellular model of Joubert syndrome reveals ciliary defects which can be rescued with targeted therapies.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Clinical, genetic and bioinformatic analysis of Saudi families with Joubert syndrome and related disorders.Human genomics · 2026Article
- Urinary renal epithelial cells can be used for NPHP1 phenotyping and a personalized therapeutic strategy.Journal of cell science · 2025Article
- CEP290 deficiency disrupts ciliary axonemal architecture in human iPSC-derived brain organoids.Journal of cell science · 2025Article
- Urine-derived renal epithelial cells for deep phenotyping and transcriptomic response to therapy in Fabry disease.Clinical science (London, England : 1979) · 2025Article
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- Nephronophthisis: a pathological and genetic perspective.Pediatric nephrology (Berlin, Germany) · 2024Review
- Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.Cell and tissue research · 2024Article
- Ciliary phenotyping in renal epithelial cells in a cranioectodermal dysplasia patient withFrontiers in molecular biosciences · 2023Article
- The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies.Annual review of genomics and human genetics · 2022Review
- Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.American journal of human genetics · 2022Article
- Phenotypic characterization of Cdkl5-knockdown neurons establishes elongated cilia as a functional assay for CDKL5 Deficiency Disorder.Neuroscience research · 2022Article
- Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia.The EMBO journal · 2022Article
- ARL3, a small GTPase with a functionally conserved role in primary cilia and immune synapses.Small GTPases · 2021Review
- Aquatic models of human ciliary diseases.Genesis (New York, N.Y. : 2000) · 2021Review
- Intraflagellar Transport Proteins as Regulators of Primary Cilia Length.Frontiers in cell and developmental biology · 2021Review
- Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis.Frontiers in cell and developmental biology · 2021Review
- Updating the Genetic Landscape of Inherited Retinal Dystrophies.Frontiers in cell and developmental biology · 2021Article
- Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development.BMC developmental biology · 2020Article
- Use of patient derived urine renal epithelial cells to confirm pathogenicity of PKHD1 alleles.BMC nephrology · 2020Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Joubert syndrome (JBTS) is the archetypal ciliopathy caused by mutation of genes encoding ciliary proteins leading to multi-system phenotypes, including a cerebello-retinal-renal syndrome. JBTS is genetically heterogeneous, however mutations in CEP290 are a common underlying cause. The renal manifestation of JBTS is a juvenile-onset cystic kidney disease, known as nephronophthisis, typically progressing to end-stage renal failure within the first two decades of life, thus providing a potential window for therapeutic intervention. In order to increase understanding of JBTS and its associated kidney disease and to explore potential treatments, we conducted a comprehensive analysis of primary renal epithelial cells directly isolated from patient urine (human urine-derived renal epithelial cells, hURECs). We demonstrate that hURECs from a JBTS patient with renal disease have elongated and disorganized primary cilia and that this ciliary phenotype is specifically associated with an absence of CEP290 protein. Treatment with the Sonic hedgehog (Shh) pathway agonist purmorphamine or cyclin-dependent kinase inhibition (using roscovitine and siRNA directed towards cyclin-dependent kinase 5) ameliorated the cilia phenotype. In addition, purmorphamine treatment was shown to reduce cyclin-dependent kinase 5 in patient cells, suggesting a convergence of these signalling pathways. To our knowledge, this is the most extensive analysis of primary renal epithelial cells from JBTS patients to date. It demonstrates the feasibility and power of this approach to directly assess the consequences of patient-specific mutations in a physiologically relevant context and a previously unrecognized convergence of Shh agonism and cyclin-dependent kinase inhibition as potential therapeutic targets.
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