Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder.

ABSTRACT: The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.

SUBMITTER: Kuukasjarvi A

PROVIDER: S-EPMC8633184 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Dystonia Associated with Idiopathic Slow Orthostatic Tremor.

Project description:BACKGROUND:We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. CASE REPORT:The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4-8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. DISCUSSION:Slow orthostatic tremor may be associated with dystonia and dystonic tremor.

| S-EPMC4749092 | biostudies-literature

Ocular palatal tremor plus dystonia - new syndromic association.

Project description:ObjectiveOcular palatal tremor typically develops after a breach in the Guillian-Mollaret triangle. We herein describe a variant of this syndrome in which dystonia is also present, hence called, here, ocular palatal tremor plus dystonia.MethodsWe assessed eye-head movements and dystonia in six patients with ocular palatal plus dystonia.ResultsAmong six patients with ocular palatal tremor two had focal dystonia, three had multifocal dystonia, and one had generalized dystonia. The dystonia affected the upper extremities and neck in four patients, the lower extremities in three and the face in two. Three out of four cervical dystonia patients had head tremor. Two patients also had speech involvement. Lack of correlation between eye and head oscillations suggested that head oscillations were not compensatory or secondary to the eye oscillations and vice versa.ConclusionsWe describe a novel variant of ocular palatal tremor with dystonia. We speculate that in such variant the dystonia is possibly could be a result of abnormal cerebellar outflow in patients with a breach in Guillain-Mollaret triangle.

| S-EPMC4753074 | biostudies-literature

Head tremor at disease onset: an ataxic phenotype of cervical dystonia.

Project description:BackgroundCervical dystonia (CD) can present with head tremor. It is unclear whether ataxic features are differentially associated with this phenotype at onset of CD.ObjectivesWe sought to evaluate: (1) the demographic features of CD patients with (Tr-CD) and without head tremor (nTr-CD) at onset, and (2) the differential ataxic features between these CD subtypes.MethodsFor the first objective, we compared demographic data in Tr-CD versus nTr-CD subtypes in the entire cohort of CD subjects enrolled in the Dystonia Coalition Natural History and Biorepository studies (n = 1608). For the second objective, we rated the standardized videos from consecutively enrolled Tr-CD subjects (n = 50) and age-, gender-, and disease duration-matched nTr-CD subjects (n = 50) for ataxia severity scoring using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS); and for dystonia severity using the Toronto Western Spasmodic Torticollis Rating Scale section-I (TWSTRS) and the Global Dystonia Rating Scale (GDRS).ResultsOf 1,608 subjects, 18.1% (n = 291) were classified as Tr-CD and 81.9% (n = 1317) as nTr-CD. The Tr-CD cohort was older, predominantly female, and had longer disease duration than the nTr-CD cohort (p = 0.01). Compared to nTr-CD, Tr-CD subjects had worse generalized ataxia, speech, and gait and posture scores. High ataxia severity with low dystonia severity distinguished Tr-CD from nTr-CD with high accuracy (area under the curve, 0.91 (95% CI 0.85-0.97).ConclusionsHead tremor at disease onset represents a clinically distinguishable subtype of cervical dystonia affecting predominantly older women, with worse ataxia and milder dystonia than the non-tremulous dystonic phenotype.

| S-EPMC6642013 | biostudies-literature

Neurodegeneration with Progressive Dystonia: Juvenile-Onset Tay-Sachs Disease.

Project description: Not available

| S-EPMC9175441 | biostudies-literature

Tremor-Dominant Pantothenate Kinase-associated Neurodegeneration.

Project description:Neurodegeneration with brain iron accumulation (NBIA) includes a rare and heterogeneous group of disorders characterized by iron deposition in the basal ganglia. Pantothenate kinase-associated neurodegeneration (PKAN) is the most common NBIA and has 2 main presentations: typical and atypical, the latter rarely presents with tremor. Our reported patients underwent full neurologic examination, standard brain magnetic imaging, and genetic testing for PKAN. Three patients who had "tremor-dominant" PKAN with a relatively benign course were reported, including 1 with dystonic tremor and 2 with parkinsonian tremor. All 3 patients had homozygous mutations in the PANK2 gene and typical eye of the tiger sign on brain imaging. PKAN (and NBIA in general) may be a potential cause of tremor, thus emphasizing the need to consider this diagnosis even in patients with a clinical diagnosis of essential, dystonic, or parkinsonian tremor.

| S-EPMC6353413 | biostudies-literature

Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq.

Project description:A large Caucasian family is presented, in which a juvenile-onset form of open-angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected family members were identified from 31 at-risk individuals descended from the affected founder. Affected patients developed high intraocular pressures (sometimes > 40 mm Hg) within the first 2 decades of life. Linkage analysis between the disease phenotype and 12 microsatellite repeat markers located on chromosome 1q gave a maximum lod score of 8.38 at a recombination fraction of zero for marker D1S210. Analysis of recombinant haplotypes suggests a total inclusion region of about 14 cM between markers D1S194 and D1S218 at 1q21-q31. This represents the second juvenile-glaucoma family, in which the disease has been mapped to the long arm of chromosome 1.

| S-EPMC1918066 | biostudies-other

A Case of New Onset Cervical Dystonia in Pregnancy.

Project description:BackgroundThough uncommon, primary movement disorders can occur in pregnancy, the most common being restless legs syndrome and chorea gravidarum [1]. New onset dystonia in pregnancy has been reported four times previously with a resolution of symptoms within six months of delivery [2345]. Exacerbation of pre-existing movement disorders and the onset of de novo movement disorders during pregnancy support the hypothesis that female sex hormones play an important role in the regulation of basal ganglia circuitry.Case reportHere we describe a case of new-onset cervical dystonia during pregnancy with persistence of symptoms after delivery.DiscussionThe phenotypic overlap between this case and previously reported cases further establishes dystonia gravidarum as a distinct clinical entity.

| S-EPMC9783953 | biostudies-literature

Head tremor and pain in cervical dystonia.

Project description:BackgroundAlthough head tremor (HT) and pain are prevalent in cervical dystonia (CD), their joint relationship to phenotypic features of focal dystonia remains unclear.ObjectivesWe examined how severity of HT and pain are associated with age of CD onset and duration, and whether HT subtypes ("jerky" or "regular") exhibit distinct relationships between severity of HT and pain.MethodsThe severity of HT and pain were assessed with the Toronto Western Spasmodic Torticollis Rating Scale in retrospective review of 188 CD patients recruited through the Dystonia Coalition.ResultsHT severity was associated with longer CD duration (p < 0.0005), whereas pain severity was associated with younger age at onset (p = 0.043). HT severity and pain severity were not correlated for jerky HT (p = 0.996), but positively correlated for regular HT (p = 0.01).ConclusionsThe distinct associations of HT and pain with age at onset, disease duration, and HT subtype further characterize the heterogeneity of CD's clinical presentation and suggest similarly heterogeneous underlying mechanisms.

| S-EPMC8076053 | biostudies-literature

Holmes Tremor-Like Phenotype in DYT1 Dystonia.

Project description: Not available

| S-EPMC6336283 | biostudies-literature

KIF1C Variants Are Associated with Hypomyelination, Ataxia, Tremor, and Dystonia in Fraternal Twins.

Project description:KIF1C (Kinesin Family Member 1C) variants have been associated with hereditary spastic paraplegia and spastic ataxia. We report fraternal twins presenting with cerebellar ataxia and dystonic tremor. Their brain MRI showed a hypomyelinating leukoencephalopathy. Whole exome sequencing identified a homozygous KIF1C variant in both patients. KIF1C variants can manifest as a complex movement disorder with cerebellar ataxia and dystonic tremor. KIF1C variants may also cause a hypomyelinating leukoencephalopathy.

| S-EPMC6692767 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data