ArticleJournal of molecular neuroscience : MN2020
Unraveling Molecular Mechanisms of THAP1 Missense Mutations in DYT6 Dystonia.
Article in Journal of molecular neuroscience : MN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Expanding the phenotypic spectrum of THAP1 dystonia: a scoping review with an illustrative case of late-onset focal limb dystonia.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration.Open biology · 2025Article
- Mutation of the Thap4 gene causes dwarfism and testicular anomalies in rats and mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- DYT-THAP1: exploring gene expression in fibroblasts for potential biomarker discovery.Neurogenetics · 2024Article
- Synaptic Dysfunction in Dystonia: Update From Experimental Models.Current neuropharmacology · 2023Review
- Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia.Dystonia (Lausanne, Switzerland) · 2023Article
- Intronic enhancers of the humanScience advances · 2022Article
- Emerging role of a systems biology approach to elucidate factors of reduced penetrance: transcriptional changes inMedizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022Article
- A pathogenic DYT-THAP1 dystonia mutation causes hypomyelination and loss of YY1 binding.Human molecular genetics · 2022Article
- The dystonia gene THAP1 controls DNA double-strand break repair choice.Molecular cell · 2021Article
- Isolated dystonia: clinical and genetic updates.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Reduced Expression of GABAFrontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) are responsible for DYT6 dystonia. Until now, more than eighty different mutations in THAP1 gene have been found in patients with primary dystonia, and two third of them are missense mutations. The potential pathogeneses of these missense mutations in human are largely elusive. In the present study, we generated stable transfected human neuronal cell lines expressing wild-type or mutated THAP1 proteins found in DYT6 patients. Transcriptional profiling using microarrays revealed a set of 28 common genes dysregulated in two mutated THAP1 (S21T and F81L) overexpression cell lines suggesting a common mechanism of these mutations. ChIP-seq showed that THAP1 can bind to the promoter of one of these genes, superoxide dismutase 2 (SOD2). Overexpression of THAP1 in SK-N-AS cells resulted in increased SOD2 protein expression, whereas fibroblasts from THAP1 patients have less SOD2 expression, which indicates that SOD2 is a direct target gene of THAP1. In addition, we show that some THAP1 mutations (C54Y and F81L) decrease the protein stability which might also be responsible for altered transcription regulation due to dosage insufficiency. Taking together, the current study showed different potential pathogenic mechanisms of THAP1 mutations which lead to the same consequence of DYT6 dystonia.
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