Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the human alpha1A-calcium channel gene. In this section, recent advances regarding pathogenic mechanism underlying in SCA6 is presented. When human alpha1A-calcium channel gene with expanded CAG repeat is transfected into HEK cells, the voltage dependence of inactivation shifting negatively 6 to 11 mV was observed, indicating that calcium influx across plasma membrane is reduced. When alpha1A-calcium channel protein and polyglutamine stretch are examined in SCA6 brain by immunohistochemistry, formations of aggregations within the cytoplasm of SCA6 Purkinje cells were seen. These findings may indicate that both alteration of calcium channel function and formation of protein aggregation are involved in the pathogenic mechanism of SCA6.
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PMID:[Spinocerebellar ataxia type 6]. 1577 62

Spinocerebellar ataxia type 8 (SCA8) is caused by the expansion of CTA/CTG triplet repeats on 13q21. Cases can be familial or sporadic. The clinical findings include cerebellar ataxia with upper motor neuron dysfunction, dysphagia, peripheral sensory disturbances, or cognitive and psychiatric impairments, indicating phenotypic variability in SCA8. We report on a patient with rapidly progressive parkinsonism-plus syndrome resembling corticobasal degeneration and triplet expansions in the SCA8 locus. The relationship between clinical phenotype and triplet expansions in the SCA8 locus requires further study.
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PMID:Sporadic SCA8 mutation resembling corticobasal degeneration. 1636 57

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited ataxia caused by expansion of ATTCT pentanucleotide repeat in intron 9 of a novel gene, E46L, on chromosome 22q13.3. SCA10 is a complex neurodegenerative condition. Initial studies characterized SCA10 as pure cerebellar ataxia associated with seizures. Recent identification of new SCA10 families revealed more diverse phenotypes, including polyneuropathy, pyramidal signs, cognitive and neuropsychiatric impairment. Moreover, several families manifest with ataxia without seizures. Thus a complete clinical spectrum is emerging. Progress has also been made in understanding the molecular and genetic mechanisms of pathogenesis. The length of expanded ATTCT repeats is variable in different tissues and highly unstable during paternal transmission, revealing complex genetic and pathogenetic processes. Under torsional stress, ATTCT repeats form unpaired DNA structure and may serve as an erroneous DNA replication origin, potentially contributing to repeat instability and aberrant cell cycle entry. E46L is a cytoplasmic protein with unknown function. Reduced expression of E46L in primary neuronal cultures from cerebellum and cortex by small interfering RNAs (siRNAs) caused increased apoptosis, raising the possibility that reduced expression of E46L might also play an important role in SCA10 pathogenesis.
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PMID:Recent progress in spinocerebellar ataxia type-10 (SCA10). 1589 57

Spinocerebellar ataxia 13 is a slowly progressive and relatively pure autosomal dominant cerebellar ataxia with childhood onset and mental deficiency. The responsible gene has been assigned to a 5.2 Mbases interval on chromosome 19q in a single French family.
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PMID:Spinocerebellar ataxia with mental retardation (SCA13). 1589 58

Spinocerebellar ataxia 25 (SCA25) is a rare form of autosomal dominant cerebellar ataxia associated with a severe sensory neuropathy. Clinical variability ranges from incomplete penetrance at age 61 to a Friedreich ataxia-like syndrome. The responsible locus was mapped to chromosome 2p in a large region of 14 Mbases in a single French kindred.
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PMID:Spinocerebellar ataxia with sensory neuropathy (SCA25). 1589 62

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disease characterized by various symptoms including cerebellar ataxia. Recently, several missense mutations in the protein kinase Cgamma (gammaPKC) gene have been found in different SCA14 families. To elucidate how the mutant gammaPKC causes SCA14, we examined the molecular properties of seven mutant (H101Y, G118D, S119P, S119F, Q127R, G128D, and F643L) gammaPKCs fused with green fluorescent protein (gammaPKC-GFP). Wild-type gammaPKC-GFP was expressed ubiquitously in the cytoplasm of CHO cells, whereas mutant gammaPKC-GFP tended to aggregate in the cytoplasm. The insolubility of mutant gammaPKC-GFP to Triton X-100 was increased and correlated with the extent of aggregation. gammaPKC-GFP in the Triton-insoluble fraction was rarely phosphorylated at Thr(514), whereas gammaPKC-GFP in the Triton-soluble fraction was phosphorylated. Furthermore, the stimulation of the P2Y receptor triggered the rapid aggregation of mutant gammaPKC-GFP within 10 min after transient translocation to the plasma membrane. Overexpression of the mutant gammaPKC-GFP caused cell death that was more prominent than wild type. The cytotoxicity was exacerbated in parallel with the expression level of the mutant. These results indicate that SCA14 mutations make gammaPKC form cytoplasmic aggregates, suggesting the involvement of this property in the etiology of SCA14.
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PMID:Mutant protein kinase Cgamma found in spinocerebellar ataxia type 14 is susceptible to aggregation and causes cell death. 1596 45

Spinocerebellar ataxia type 6 (SCA-6) is a rare, autosomal dominant neurodegenerative condition characterized by adult onset cerebellar ataxia and ocular movement disorders. The presentation is non-specific, and radiological characterization would be of diagnostic benefit. There is little published on the radiological appearances of SCA-6, and there are conflicting reports in the literature. We report the radiological findings in a group of 10 patients with SCA-6.
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PMID:Radiological characterization of spinocerebellar ataxia type 6. 1604 19

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for approximately 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.
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PMID:Evidence of a common founder for SCA12 in the Indian population. 1613 11

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder, first described in a Japanese family, showing linkage to chromosome 19q13.4-qter. Recently, mutations have been identified in the PRKCG gene in families with SCA14. The PRKCG gene encodes the protein kinase Cgamma (PKCgamma), a member of a serine/threonine kinase family involved in signal transduction important for several cellular processes, including cell proliferation and synaptic transmission. To identify the disease-causing mutation in a large group of ataxia patients, we searched for mutations in the PRKCG gene. We ascertained 366 unrelated patients with spinocerebellar ataxia, either pure or with associated features such as epilepsy, mental retardation, seizures, paraplegia, and tremor. A C-to-G transversion in exon 4, resulting in a histidine-to-glutamine change at codon 101 of the PKCgamma protein, was identified in patients from a family with slowly progressive pure cerebellar ataxia. Functional studies performed in HEK293 cells transfected with normal or mutant construct showed that this mutation affects PKCgamma stability or solubility, verified by time-dependent decreased protein levels in cell culture. In conclusion, the H101Q mutation causes slowly progressive uncomplicated ataxia by interfering with PKCgamma stability or solubility, which consequently may cause in either case a decrease in the overall PKCgamma-dependent phosphorylation.
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PMID:A novel H101Q mutation causes PKCgamma loss in spinocerebellar ataxia type 14. 1618 24

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominantly inherited disorder characterized by cerebellar ataxia, dysarthria and nystagmus. The molecular background for the disorder is a CAG repeat expansion in the CACNA1A gene located on chromosome 19. The size of SCA6 expanded alleles is usually stable, and variation in repeat size over successive generations is rare. We report a Danish family with one case of SCA6 resembling a sporadic case of spinocerebellar ataxia. Analysis of the CACNA1A gene showed meiotic CAG repeat instability in the transmission from a 70-year-old woman with no subjective symptoms to her symptomatic son. The CAG repeat size expanded from 22 repeats in the mother to 23 repeats in the proband. This case demonstrates maternal repeat instability and clinical anticipation in a family with SCA6.
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PMID:Meiotic CAG repeat instability in spinocerebellar ataxia type 6: maternally transmitted elongation in a presumed sporadic case. 1631 Aug 5


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