Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DRPLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD.
 ...
PMID:Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease. 1475 71

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
 ...
PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

We report a family with 16q-ADCA(16q 22.1 linked autosomal dominant cerebellar ataxia) coexisting with SCA8 repeat expansion. The brothers in this family presented with pyramidal signs, tremor, myoclonus and mental retardation in addition to cerebellar symptom in childhood. They showed both C-to-T substitution puratrophin-1 gene and an expanded allele of the SCA8 gene in the brothers and their father. These siblings presented with atypical symptoms and early onset age as16q-ADCA. Although it remains controversial whether the expanded SCA8 allele is associated with cerebellar symptoms, the coexistence of SCA8 repeat expansion with SCA6 was reported previously. Pure or predominant cerebellar symptoms were found in patients with SCA8, SCA6 and 16q-ADCA. In addition, common findings in neuropathology of SCA8, SCA6 and 16q-ADCA have been reported. We suppose that coexistence of SCA8 repeat expansion with 16q-ADCA may be involved in the pathogenesis and severe symptoms in this family.
 ...
PMID:Severe symptoms of 16q-ADCA coexisting with SCA8 repeat expansion. 1868 74

We report the case of a 29 year old woman with a complex movement disorder syndrome due to the combination of coexisting pathological triplet repeat expansions of huntingtin and ATXN8 genes. The disease course was characterized by mental disturbances including cognitive decline and changes in personality starting at the age of 12 years, followed by twisting motions, intentional tremor and gait ataxia. Later Parkinsonian symptoms of micrographia, bradykinesia, muscle rigidity and mental decline became dominant. Brain MRI showed hypoplasia of the nucleus caudatus and generalized atrophy; MR spectroscopy revealed a decrease of all typical metabolites except for an increased level of lactate and acetate. Therapeutic trials with pramipexole, ropinirole and tetrabenazine showed no benefit, while levetiracetam caused agitation and hallucinations. We discuss phenotype-genotype correlation and the rule of triplet repeat expansions of gene ATXN8.
 ...
PMID:Coexisting huntingtin and SCA8 repeat expansion: case report of a severe complex neurodegenerative syndrome. 2040 8

A 31-year-old man was referred to our hospital because of progressive tremor and clumsiness in his limbs and trunk. His symptoms were started in the right leg then gradually spread to all extremities as well as his trunk for 2 years. Neurological examinations revealed muscle rigidity with resting tremor predominantly right limbs. Akinesia and retropulsion were positive. Neither pyramidal tract sign nor cerebellar ataxia was detected. Genetic testing showed the expansion of SCA8 CTA/CTG repeats as 28/141 repeats. Though moderate expansion (less than 92) of SCA8 repeats has been reported in healthy subjects and patients with various diseases, the extraordinary long expansion of CTA/CTG repeats in SCA8 gene in our patient could be significantly pathological. 600 mg/day of L-DOPA clearly improved his symptoms. Dedicate follow up of the clinical course of our patient and the accumulation of the further cases is essential.
 ...
PMID:[A case of juvenile parkinsonism with expanded SCA8 CTA/CTG repeats]. 2360 41

Trinucleotide repeat disorders comprise a variable group of inherited neurodegenerative diseases, with a large range in prevalence figures. There is a broad range in clinical presentations, but many of these diseases lead to some form of ataxia or other movement disorders, which are frequently combined with cognitive or psychiatric disturbances. This group can be divided into CAG- versus non-CAG-repeat diseases. Apart from spinocerebellar ataxia type 6 and 12 (SCA6 and SCA12), these CAG-repeat diseases, as well as Huntington disease-like 2 (HDL2) and SCA8, can be neuropathologically identified using 1C2 polyglutamine antibodies. In fragile X-associated tremor and ataxia, SCA6 and SCA12 ubiquitin/p62-positive and 1C2-negative inclusion bodies can be observed. In the other diseases proteinaceous inclusions are not found. For definite diagnosis genetic analysis is necessary.
 ...
PMID:Trinucleotide repeat disorders. 2898 84