ArticleThe Journal of clinical investigation2008
Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05573984 (A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy), which is not on this map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy
Who cites it
64 citing papers in PubMed, 102 citations in OpenAlex.
- Cell-autonomous restoration of splicing homeostasis and RP11 phenotype in patient-derived RPE and retinal organoids by PRPF31.AAV gene therapy.Nature communications · 2026Article
- Characterising PRPF31-associated retinal dystrophy: Clinical insights from baseline data in a natural history study.Acta ophthalmologica · 2026Article
- Biallelic GLTP mutations cause nonsyndromic epidermal differentiation disorder via disrupted epidermal glucosylceramide transport.The Journal of clinical investigation · 2026Article
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- The RNA content of extracellular vesicles from gene-editedMolecular therapy. Methods & clinical development · 2025Article
- Population Genomics of Premature Termination Codons in Cavefish With Substantial Trait Loss.Molecular biology and evolution · 2025Article
- A Precision Therapy Approach for Retinitis Pigmentosa 11 Using Splice-Switching Antisense Oligonucleotides to Restore the Open Reading Frame of PRPF31.International journal of molecular sciences · 2024Article
- Differential co-expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia.Cancer medicine · 2023Article
- Exome sequencing in retinal dystrophy patients reveals a novel candidate gene ER membrane protein complex subunit 3.Heliyon · 2023Article
- Retinal organoids provide unique insights into molecular signatures of inherited retinal disease throughout retinogenesis.Journal of anatomy · 2023Review
- Retinitis pigmentosa-associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule cells.Life science alliance · 2023Article
- Article
- A progeroid syndrome caused by a deep intronic variant in TAPT1 is revealed by RNA/SI-NET sequencing.EMBO molecular medicine · 2023Article
- Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue.NPJ Regenerative medicine · 2022Article
- Germline Mutations for Kidney Volume in ADPKD.Kidney international reports · 2022Article
- Microtubule modification defects underlie cilium degeneration in cell models of retinitis pigmentosa associated with pre-mRNA splicing factor mutations.Frontiers in genetics · 2022Article
- Autosomal dominant retinitis pigmentosa with incomplete penetrance due to an intronic mutation of theMolecular vision · 2022Article
- Observational
- Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model.Disease models & mechanisms · 2021Article
- A hypomorphic variant in EYS detected by genome-wide association study contributes toward retinitis pigmentosa.Communications biology · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Dominant mutations in the gene encoding the mRNA splicing factor PRPF31 cause retinitis pigmentosa, a hereditary form of retinal degeneration. Most of these mutations are characterized by DNA changes that lead to premature termination codons. We investigated 6 different PRPF31 mutations, represented by single-base substitutions or microdeletions, in cell lines derived from 9 patients with dominant retinitis pigmentosa. Five of these mutations lead to premature termination codons, and 1 leads to the skipping of exon 2. Allele-specific measurement of PRPF31 transcripts revealed a strong reduction in the expression of mutant alleles. As a consequence, total PRPF31 protein abundance was decreased, and no truncated proteins were detected. Subnuclear localization of the full-length PRPF31 that was present remained unaffected. Blocking nonsense-mediated mRNA decay significantly restored the amount of mutant PRPF31 mRNA but did not restore the synthesis of mutant proteins, even in conjunction with inhibitors of protein degradation pathways. Our results indicate that most PRPF31 mutations ultimately result in null alleles through the activation of surveillance mechanisms that inactivate mutant mRNA and, possibly, proteins. Furthermore, these data provide compelling evidence that the pathogenic effect of PRPF31 mutations is likely due to haploinsufficiency rather than to gain of function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.