Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA120355 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ~30-40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms. In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia.We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers. Comparison of whole blood expression profiles of patients with DYT1 dystonia with non manifesting mutation carriers and non mutation carriers
2010-05-26 | E-GEOD-19419 | biostudies-arrayexpress
Project description:DYT-TOR1A (DYT1) is the most common monogenetic form of dystonia characterized by a reduced disease penetrance of 30-40% only. Environmental factors are suspected to play a major role in eliciting dystonia in DYT1 gene carriers. In line with this observation a sciatic nerve crush injury as a traumatic environmental stimulus was previously shown to induce dystonia-like movements (DLM) in the asymptomatic DYT-TOR1A rat model (∆ETorA). The primary objective of this study was to assess the underlying pathophysiological mechanisms associated with DYT1 dystonia using this “second hit” DYT1 rodent model. The striatum, as one of the pathophysiologic key structures of dystonia, was analysed twelve weeks after nerve injury by unbiased RNA-sequencing in order to identify differentially expressed genes (DEG) and pathways.
2024-12-31 | GSE249994 | GEO
Project description:DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ~30-40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms. In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia.We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.
2010-05-27 | GSE19419 | GEO
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2025-01-24 | E-GEOD-21369 | ExpressionAtlas
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2025-01-24 | E-GEOD-31348 | ExpressionAtlas
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2025-01-23 | E-MTAB-5638 | ExpressionAtlas
Project description:Dystonia is a centrally driven movement disorder characterized by often painful twisting motions and postures. The majority of dystonia cases are idiopathic and sporadic, although a significant number of rare inherited forms have defined genetic causes. However, regardless of etiology, the biological mechanisms for nearly all forms of dystonia are still largely unknown and there are currently no disease-modifying treatments. Here we show a common role for impaired functioning of the eIF2α stress-response pathway in rare inherited and common sporadic forms of dystonia. We first identified a potential role for the eIF2α pathway in dystonia through a genome-wide RNAi screen aimed at correcting a DYT1 dystonia-related cellular phenotype. Mechanistically, we find that the corrective effect is mediated by activating the eIF2α pathway through an eIF2α-phosphorylation and ATF4 transcription factor-dependent mechanism. We further find evidence that this pathway is impaired in DYT1 patient-derived cell lines, suggesting a role in pathogenesis. Notably, pathogenicity of reduced eIF2α pathway signaling is supported by another known cause of dystonia, DYT16, which is due to loss-of-function mutations in the PRKRA gene that encodes an eIF2α kinase activator. Here, we demonstrate that sporadic cervical dystonia patients share a rare, conserved, loss-of-function ATF4 mutation. Finally, we show that pharmacologically enhancing eIF2α signaling improves DYT1-related phenotypes in both a cultured cell system and a mouse model. Our results identify eIF2α signaling as a novel pathway in the pathogenesis of multiple forms of dystonia. Our work also shows that the eIF2α pathway constitutes an attractive biological target for the development of dystonia therapeutics.
2016-11-02 | GSE89180 | GEO
Project description:DYT1 dystonia is a neurological movement disorder characterized by a dominant 3-base pair deletion (dGAG) in the TOR1A gene. This study demonstrates a gene editing approach that selectively targets the dGAG mutation in the TOR1A DYT1 allele while safeguarding the wild-type (WT) TOR1A allele. We optimized an adeno-associated virus (AAV) vector-compatible variant of the Staphylococcus aureus Cas9 nuclease ortholog (SaCas9-KKH) in DYT1 patient-derived human neuroprecursor cells (hNPCs). On-target editing of the TOR1A DYT1 allele was confirmed at the genomic level from brain tissue in a xenograft mouse model. To avoid brain biopsy for demonstrating TOR1A DYT1 editing, we developed a non-invasive monitoring method using extracellular RNA (exRNA). TOR1A exRNA was retrieved from the EV secretions of hNPCs and plasma samples, indicating whether the donor was a TOR1A DYT1 carrier. This technique enabled us to assess AAV-mediated disruption of the TOR1A DYT1 allele in the brains of mice using blood samples
2025-03-01 | GSE288087 | GEO
Project description:Subtype-specific peripheral blood gene expression profiles in recent onset JIA
2025-01-24 | E-GEOD-13501 | ExpressionAtlas
Project description:Peripheral blood gene expression profiles in obese subjects without metabolic syndrome.
2025-01-23 | E-MTAB-3017 | ExpressionAtlas