ArticleHuman molecular genetics2015
Translational read-through of the RP2 Arg120stop mutation in patient iPSC-derived retinal pigment epithelium cells.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 104 citations in OpenAlex.
- Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification.Investigative ophthalmology & visual science · 2026Article
- Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.Cellular and molecular life sciences : CMLS · 2026Article
- Ophthalmologic Manifestations in Bardet-Biedl Syndrome: Emerging Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- A novel recurrent ARL3 variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models.Human molecular genetics · 2025Article
- Inter-chromosomal insertions at Xq27.1 associated with retinal dystrophy induce dysregulation of LINC00632 and CDR1as/ciRS-7.American journal of human genetics · 2025Article
- Genetic and Clinical Analyses of theGenes · 2024Article
- RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers.American journal of ophthalmology · 2024Article
- Cell-cell interaction in the pathogenesis of inherited retinal diseases.Frontiers in cell and developmental biology · 2024Review
- Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.Current stem cell research & therapy · 2024Review
- Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells.Frontiers in medicine · 2024Review
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Article
- Eupatilin improves cilia defects in human CEP290 ciliopathy models.bioRxiv : the preprint server for biology · 2023Article
- RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History.Ophthalmology · 2023Article
- Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook.Therapeutics and clinical risk management · 2023Review
- Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis.Stem cell reports · 2022Article
- Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses.International journal of molecular sciences · 2022Article
- A Japanese boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-associated retinal disorder.Human genome variation · 2021Article
- CRISPR-Cas9 correction ofMolecular therapy. Nucleic acids · 2021Article
- Ataluren-Promising Therapeutic Premature Termination Codon Readthrough Frontrunner.Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the RP2 gene lead to a severe form of X-linked retinitis pigmentosa. RP2 patients frequently present with nonsense mutations and no treatments are currently available to restore RP2 function. In this study, we reprogrammed fibroblasts from an RP2 patient carrying the nonsense mutation c.519C>T (p.R120X) into induced pluripotent stem cells (iPSC), and differentiated these cells into retinal pigment epithelial cells (RPE) to study the mechanisms of disease and test potential therapies. RP2 protein was undetectable in the RP2 R120X patient cells, suggesting a disease mechanism caused by complete lack of RP2 protein. The RP2 patient fibroblasts and iPSC-derived RPE cells showed phenotypic defects in IFT20 localization, Golgi cohesion and Gβ1 trafficking. These phenotypes were corrected by over-expressing GFP-tagged RP2. Using the translational read-through inducing drugs (TRIDs) G418 and PTC124 (Ataluren), we were able to restore up to 20% of endogenous, full-length RP2 protein in R120X cells. This level of restored RP2 was sufficient to reverse the cellular phenotypic defects observed in both the R120X patient fibroblasts and iPSC-RPE cells. This is the first proof-of-concept study to demonstrate successful read-through and restoration of RP2 function for the R120X nonsense mutation. The ability of the restored RP2 protein level to reverse the observed cellular phenotypes in cells lacking RP2 indicates that translational read-through could be clinically beneficial for patients.
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