ArticlePLoS genetics2018
Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- [Effects ofZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Transcriptomic profiling of DYT-TOR1A patient-derived iPSC reveals dysregulation in extracellular matrix, lipid metabolism, and Chr22q11.23.BMC medical genomics · 2025Article
- Article
- Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes.Annals of neurology · 2025Article
- The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation.Nature communications · 2025Article
- Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei.Dystonia (Lausanne, Switzerland) · 2025Article
- Mutation in Prkra results in cerebellar abnormality and reduced eIF2α phosphorylation in a model of DYT-PRKRA.Disease models & mechanisms · 2024Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- A frameshift mutation in the murinebioRxiv : the preprint server for biology · 2024Article
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- DYT-THAP1: exploring gene expression in fibroblasts for potential biomarker discovery.Neurogenetics · 2024Article
- The integrated stress response pathway and neuromodulator signaling in the brain: lessons learned from dystonia.The Journal of clinical investigation · 2024Review
- Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia.Dystonia (Lausanne, Switzerland) · 2023Article
- DYT-Frontiers in neuroscience · 2023Review
- Synaptic Dysfunction in Dystonia: Update From Experimental Models.Current neuropharmacology · 2023Review
- DYT-TOR1A genotype alters extracellular vesicle composition in murine cell model and shows potential for biomarker discovery.Dystonia (Lausanne, Switzerland) · 2023Article
- Potential interactions between cerebellar dysfunction and sleep disturbances in dystonia.Dystonia (Lausanne, Switzerland) · 2022Article
- Transgenic Mice for the Translational Study of Neuropathic Pain and Dystonia.International journal of molecular sciences · 2022Review
- Genetic screening in patients of Meige syndrome and blepharospasm.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Dystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1 [THAP (Thanatos-associated protein) domain containing, apoptosis associated protein 1], a ubiquitously expressed transcription factor with DNA binding and protein-interaction domains, cause dystonia, DYT6. There is a unique, neuronal 50-kDa Thap1-like immunoreactive species, and Thap1 levels are auto-regulated on the mRNA level. However, THAP1 downstream targets in neurons, and the mechanism via which it causes dystonia are largely unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1 C54Y or ΔExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2α Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic LongTerm Depression, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays were consistent with those enrichments, and the plasticity defects were partially corrected by salubrinal. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence in the pathophysiology of several forms of inherited dystonia.
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