ArticleProceedings of the National Academy of Sciences of the United States of America2023
Glial dysregulation in the human brain in fragile X-associated tremor/ataxia syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Variable expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Pooled it
- MECP2Science China. Life sciences · 2026Article
- Advances in the Comprehensive Tree Shrew Brain Atlas.Biomolecules · 2026Review
- DNA Methylation and Proteomic Profiling of Postmortem Brain Tissue Reveals Epigenetic Dysregulation and Neuroinflammatory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).bioRxiv : the preprint server for biology · 2026Article
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of FMR1 mRNA structure on the efficiency of non-canonical translation of toxic polyglycine protein.Nucleic acids research · 2026Article
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- Metabolic reprogramming during human neuron differentiation indicates glutaminase as a key determinant in Fragile X syndrome.Cell reports · 2026Article
- Integrative transcriptome-wide association analyses reveal PRKCG-linked GABAergic dysfunction in Fragile X-associated tremor/ataxia syndrome.Nature communications · 2026Article
- Glymphatic dysfunction and neuroinflammation in FXTAS: evidence from DTI-ALPS and gene expression analysis.Frontiers in molecular neuroscience · 2026Article
- Essential tremor-like phenotype in Fragile X carrier women.Clinical parkinsonism & related disorders · 2026Article
- Long-read sequencing reveals extensivebioRxiv : the preprint server for biology · 2025Article
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- Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders.Science (New York, N.Y.) · 2025Article
- Reduced Respiratory Sinus Arrhythmia in Infants with theInternational journal of molecular sciences · 2025Article
- Beyond the Synapse:International journal of molecular sciences · 2024Review
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain.American journal of human genetics · 2024Article
- Social Communication Delay in an Unbiased Sample of Preschoolers With theJournal of speech, language, and hearing research : JSLHR · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Short trinucleotide expansions at the FMR1 locus are associated with the late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from fragile X syndrome (associated with longer expansions), with no clear molecular explanation for these marked differences. One prevailing theory posits that the shorter, premutation expansion uniquely causes extreme neurotoxic increases in FMR1 mRNA (i.e., four to eightfold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single-nucleus RNA sequencing to postmortem frontal cortex and cerebellum from 7 individuals with premutation and matched controls (n = 6) to assess cell type-specific molecular neuropathology. We found only modest upregulation (~1.3-fold) of FMR1 in some glial populations associated with premutation expansions. In premutation cases, we also identified decreased astrocyte proportions in the cortex. Differential expression and gene ontology analysis demonstrated altered neuroregulatory roles of glia. Using network analyses, we identified cell type-specific and region-specific patterns of FMR1 protein target gene dysregulation unique to premutation cases, with notable network dysregulation in the cortical oligodendrocyte lineage. We used pseudotime trajectory analysis to determine how oligodendrocyte development was altered and identified differences in early gene expression in oligodendrocyte trajectories in premutation cases specifically, implicating early cortical glial developmental perturbations. These findings challenge dogma regarding extremely elevated
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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.