ArticleEMBO molecular medicine2021
CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Large-scale genetic profiling of hereditary ataxias in China: implications for a stepwise molecular diagnostic strategy.Translational neurodegeneration · 2026Article
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- Population-scale disease-associated tandem repeat analysis reveals locus and ancestry-specific insights.Nature communications · 2026Article
- Comprehensive Characterization of Clinical Phenotypes and CTG Repeat-Associated Manifestations in Spinocerebellar Ataxia Type 8.Cerebellum (London, England) · 2026Article
- Novel Imaging Phenotype in Spinal Cerebellar Ataxia Type 8: Symmetrical White Matter Changes without Cerebellar Atrophy.Cerebellum (London, England) · 2026Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Unmasking cerebellar disease: functional neurologic disorder as a precursor to spinocerebellar ataxia type 8.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Modeling neuronal intranuclear inclusion disease: A review of animal and human-derived cellular models and mechanistic insights.Zoological research · 2025Review
- A genome-wide approach for the discovery of novel repeat expansion disorders in the Undiagnosed Diseases Network cohort.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- STRchive: a dynamic resource detailing population-level and locus-specific insights at tandem repeat disease loci.Genome medicine · 2025Article
- Cerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8).Neurobiology of disease · 2025Article
- Article
- Review
- Spinocerebellar ataxias masquerading as movement disorders: clinical and genetic characterization.Frontiers in neurology · 2025Article
- NOTCH2NLC GGC intermediate repeat with serine induces hypermyelination and early Parkinson's disease-like phenotypes in mice.Molecular neurodegeneration · 2024Article
- The Potential of Mesenchymal Stem Cells in Treating Spinocerebellar Ataxia: Advances and Future Directions.Biomedicines · 2024Review
- Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.Nature reviews. Genetics · 2024Review
- Cerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8).bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Short tandem repeat expansions in sporadic amyotrophic lateral sclerosis and frontotemporal dementia.Science advances · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 10 institutions in 4 countries.
Funding
Abstract
Spinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG•CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia. To understand the variable penetrance of SCA8, we studied the molecular differences between highly penetrant families and more common sporadic cases (82%) using a large cohort of SCA8 families (n = 77). We show that repeat expansion mutations from individuals with multiple affected family members have CCG•CGG interruptions at a higher frequency than sporadic SCA8 cases and that the number of CCG•CGG interruptions correlates with age at onset. At the molecular level, CCG•CGG interruptions increase RNA hairpin stability, and in cell culture experiments, increase p-eIF2α and polyAla and polySer RAN protein levels. Additionally, CCG•CGG interruptions, which encode arginine interruptions in the polyGln frame, increase toxicity of the resulting proteins. In summary, SCA8 CCG•CGG interruptions increase polyAla and polySer RAN protein levels, polyGln protein toxicity, and disease penetrance and provide novel insight into the molecular differences between SCA8 families with high vs. low disease penetrance.
Indexed as
Identifiers
What OpenQuestion holds
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.