Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE43771 | GEO | 2013/01/26
SECONDARY ACCESSION(S): PRJNA187370
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression studies were performed to identify pathways possibly dysregulated by mutant in the gene GM-NM-1(olf). These experiments employed RNA derived from lymphoblastoid cell lines established for 4 affected carriers and 4 non-carriers. In comparison to endogenous control and other dystonia-associated genes, GNAL was expressed at relatively low levels in lymphoblastoid cell lines. Comparison of whole blood expression profiles of mutation carrying dystonia patients with normal controls
2013-01-26 | E-GEOD-43771 | biostudies-arrayexpress
Project description:The vast majority of patients with primary dystonia are adults with focal or segmental distribution of involuntary movements. Although ~10% of probands have at least one first- or second-degree relative to dystonia, large families suited for linkage analysis are exceptional. After excluding mutations in known primary dystonia genes (TOR1A, THAP1 and CIZ1), whole-exome sequencing identified a GNAL missense mutation (c.682G>T, p.V228F) in an African-American pedigree with clinical phenotypes that include cervical, laryngeal and hand-forearm dystonia. Screening of 760 subjects with familial and sporadic primary dystonia identified three Caucasian pedigrees with GNAL mutations [c.591dupA (p.R198Tfs*13); c.733C>T (p.R245*); and c.3G>A (p.M1?)]. These mutations show incomplete penetrance. Our findings corroborate those of a recent study which used whole-exome sequencing to identify missense and nonsense GNAL mutations in Caucasian pedigrees of mixed European ancestry with mainly adult-onset cervical and segmental dystonia. GNAL encodes guanine nucleotide-binding protein G(olf), subunit alpha [Gα(olf)]. Gα(olf) plays a role in olfaction, coupling D1 and A2a receptors to adenylyl cyclase, and histone H3 phosphorylation. African-American subjects harboring the p.V228F mutation exhibited microsmia. Lymphoblastoid cell lines from subjects with the p.V228F mutation showed upregulation of genes involved in cell cycle control and development. Consistent with known sites of network pathology in dystonia, immunohistochemical studies indicated that Gα(olf) is highly expressed in the striatum and cerebellar Purkinje cells, and co-localized with corticotropin-releasing hormone receptors in the latter.
| S-EPMC3658169 | biostudies-literature
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:Ossification of the ligamentum flava (OLF) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. Although studies have identified several genes that correlated with OLF, the underlying regulation network is far from clear. To identify transcriptional regulators for OLF, we compared the circRNAs expression of the ligamentum flava tissues from OLF patients and healthy volunteers through microarray analysis, which revealed a panel of circRNAs that were specifically regulated in ligament tissues of human undergoing ossification. To identify transcriptional regulators for OLF, we compared the circRNAs expression of the ligamentum flava tissues from OLF patients and healthy volunteers through microarray analysis.
2017-10-27 | GSE106255 | GEO
Project description:Ossification of the ligamentum flava (OLF) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. Although studies have identified several genes that correlated with OLF, the underlying regulation network is far from clear. To identify transcriptional regulators for OLF, we compared the microRNA expression of the ligamentum flava tissues from OLF patients and healthy volunteers through microRNA sequencing.
2017-10-27 | GSE106256 | GEO
Project description:Ossification of the ligamentum flava (OLF) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. Although studies have identified several genes that correlated with OLF, the underlying regulation network is far from clear. To identify transcriptional regulators for OLF, we compared the lncRNAs and mRNAs expression of the ligamentum flava tissues from OLF patients and healthy volunteers through microarray analysis, which revealed a panel of lncRNAs and mRNAs that were specifically regulated in ligament tissues of human undergoing ossification. To identify transcriptional regulators for OLF, we compared the lncRNAs and mRNAs expression of the ligamentum flava tissues from OLF patients and healthy volunteers through microarray analysis.
2017-10-27 | GSE106253 | GEO
Project description:Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia
| PRJNA187370 | ENA
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
Project description:Spinal interneurons are critical modulators of locomotor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. While deficits in presynaptic inhibition have been inferred in human locomotor diseases, including dystonia, it remains unknown whether GABApre circuit components are altered in these conditions. In this study, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord. Using a microarray screen to identify genes expressed in this intermediate population, we find the kelch-like family member Klhl14, implicated in dystonia through its direct binding with torsion-dystonia related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14 and Tor1a binding is disrupted (Dyt1ΔE), GABApre-sensory afferent synapse formation is impaired. Our findings suggest a potential contribution of GABApre neurons to the deficits in presynaptic inhibition observed in dystonia.
2017-06-03 | GSE99590 | GEO