Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nocturnal myoclonus syndrome (NMS) consists of stereotyped, repetitive jerks of the lower limbs that occur during sleep or wakefulness. NMS is often related with restless-legs syndrome (RLS) and can cause severe sleep disturbances and daytime sleepiness. The efficacy of dopamine agonists in the treatment points to a dopaminergic dysfunction in NMS. We investigated the central dopamine D2-receptor occupancy with [123I] labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) ([123I]IBZM) and single photon emission tomography (SPET) in 20 patients with NMS and in 10 healthy controls. In most of the patients with NMS there was a lower [123I]IBZM binding in the striatal structures compared to controls. The results indicate that NMS is related to a decrease of central D2-receptor occupancy.
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PMID:Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration. 778 13

The paper gives a brief review of the existing literature concerning the nocturnal myoclonus syndrome (NMS). The clinical symptomatology, criteria for differential diagnosis and the relation to the restless legs syndrome (RLS) are discussed. Recently we investigated central dopamine receptor density with 123I-labeled 3'-iodo-6-methoxybenzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) and single photon emission tomography (SPECT) in patients with NMS and found a reduced density of dopamine D2-receptors in the striatal structures, indicating a dopaminergic dysfunction in NMS and RLS. We present a report concerning a 58-year old female with NMS-associated insomnia and present IBZM SPECTs and hypnograms before and after a 3-month treatment with L-dopa and discuss the results with regard to pathophysiological theories.
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PMID:[Nightly myoclonus syndrome (NMS) and restless legs syndrome (RLS)--review and case report]. 818 89

Single photon emission tomography (SPET) permits the in vivo measurements of regional cerebral radioactivity in the human brain following the administration of compounds labeled with photon-emitting isotopes. According to our SPET findings of a reduced binding of [123I]labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) to D2 dopamine receptors in striatal structures in untreated patients with nocturnal myoclonus syndrome (NMS) it seemed to be of interest to investigate whether there are changes in D2 receptor binding under dopamine replacement therapy or not. We studied the uptake and distribution of [123I]IBZM before and in the course of dopamine replacement therapy in four patients with severe insomnia caused by a nocturnal myoclonus syndrome (NMS). We found an increase of the IBZM binding to D2 receptors in the course of treatment, which was associated with an improvement of sleep quality. Reasons for this are discussed. The [123I]IBZM SPET technique in conclusion offers an intersting tool for in vivo investigations of functional changes in the dopaminergic neurotransmitter system in longitudinal studies.
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PMID:Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the course of dopamine replacement therapy in patients with nocturnal myoclonus syndrome (NMS). 857 4

Hereditary autosomal dominant myoclonus dystonia (MD) is a movement disorder characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Although various large families with MD have been described, no positive linkage has been found to a chromosomal location. We report a family with eight members with MD. Linkage analysis identified a 23-centimorgan region on chromosome 11q23 that cosegregates with the disease state (maximum multipoint logarithm of odds score = 2.96 at D11S897). This region contains an excellent candidate gene for involvement in the etiology of MD, the D2 dopamine receptor (DRD2) gene. Neurotransmission mediated by DRD2 is known to have a key role in the control of movement and also has been implicated in reward and reinforcement mechanisms and psychiatric disorders. Sequencing of the coding region of DRD2 indicated that all affected and obligate carriers were heterozygous for a Val154Ile change in exon 3 of the protein, which is highly conserved across species. This change was found neither in other unaffected members of the pedigree nor in 250 control chromosomes. Our finding provides evidence for the involvement of DRD2 in a disorder of the central nervous system and should lead to further insight into the function of the dopaminergic system in dystonia and other movement and mood disorders.
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PMID:Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. 1022 Apr 38

A novel Val154-->Ile mutation in the D2 dopamine receptor (DRD2) on chromosome 11q23 has recently been shown to be associated with myoclonus dystonia (M-D) in one large family. Sequence analysis of the DRD2 gene in 5 M-D patients from different families did not reveal any mutations, nor was there evidence of linkage to the 11q23 region in the DRD2 gene in four other families. Receptor binding and signal transduction assays of the DRD2 mutant and wild-type receptors revealed identical agonist and antagonist affinities and functional responses. These studies suggest that M-D is genetically heterogeneous. The molecular mechanisms through which the Val-->Ile mutation may contribute to M-D remain to be determined.
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PMID:Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia. 1071 58

To date, at least 12 types of primary dystonia can be distinguished on a genetic basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor in one large family (DYT11) has recently been implicated in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia (DYT8-10), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia-parkinsonism (DYT12). No positive linkage results have yet been obtained for autosomal recessive TD (DYT2) and several other families of different types of dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may occur as part of familial diseases of the basal ganglia, metabolic and storage disorders, and various X-linked and other familial neurodegenerative syndromes affecting the basal ganglia. It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.
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PMID:[Genetics of dystonia]. 1091 37

Inherited myoclonus-dystonia (IMD) is a new term used to describe an autosomal dominant form of myoclonus. Recently a family with IMD was linked to a region on chromosome 11q23 and a possible mutation identified in the D2 dopamine receptor. We have identified a large family with 12 affected individuals. Using linkage analysis and direct sequencing, the D2 receptor gene was excluded as a cause of myoclonus in this family. These results indicate that the Val154Ile D2 receptor substitution is not the universal cause of IMD. This suggests either that it is a rare, family specific polymorphism not causative of IMD, or that IMD is genetically heterogeneous.
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PMID:Inherited myoclonus-dystonia: evidence supporting genetic heterogeneity. 1121 67

Myoclonus--dystonia is a genetically heterogeneous autosomal dominant disorder caused by a mutation in the D2 dopamine receptor on chromosome 11 and a locus on chromosome 7q21-q31. The authors tested linkage to the chromosome 7q candidate region in four families with either myoclonic dystonia (n = 3) or essential myoclonus (n = 1). Age at onset ranged from 0.5 to 38 years. Only four patients from two families had a positive response to alcohol. Lod scores were positive in all four families, suggesting that chromosome 7q21-q31 is a major locus for myoclonus-dystonia with several phenotypes.
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PMID:A major locus for several phenotypes of myoclonus--dystonia on chromosome 7q. 1134 90

Currently, at least 12 types of dystonia can be distinguished on a genetic basis. Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to be associated with myoclonus-dystonia in one family. In addition, six other dystonia gene loci have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as yet been reported for autosomal recessive TD (DYT2) and in several other large families with various types of dominantly inherited TD (DYT4). It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.
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PMID:Genetics of primary dystonia. 1219 83

Several lines of biochemical and pharmacological evidence have suggested that some G-protein-coupled receptors (GPCRs) form homo oligomers, hetero oligomers or both. The GPCRs oligomerizations are considered to be related to signal transduction and some diseases. Therefore, an accurate prediction of the residues that interact upon oligomerization interface would further our understanding of signal transduction and the diseases in which GPCRs are involved. One of the complications for such a prediction is that the interfaces differ with the subtypes, even within the same GPCR family. Focusing on the distribution of residues conserved on the molecular surface in a particular subtype, we developed a new method to predict the interface for the GPCR oligomers, and applied it to several subtypes of known GPCRs to check the sensitivity. Subsequently, we found that predicted interfaces of rhodopsin, D(2) dopamine receptor and beta(2) adrenergic receptor agreed with the experimentally suggested interfaces, despite difference in the interface region among the three subtypes. Moreover, a highly conserved residue detected from the D(2) dopamine receptor corresponded to a residue involved in a missense change found in the large family of myoclonus dystonia. Our observation suggests the possibility that the disease is caused by the disorder of the oligomerization, although the molecular mechanism of the disease has not been revealed yet. The benefits and the pitfalls of the new method will be discussed, based on the results of the applications.
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PMID:Prediction of interfaces for oligomerizations of G-protein coupled receptors. 1559 72


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