Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently identified a novel SCA form in nine patients from four Japanese pedigrees through the screening for expanded polyglutamine tracts by Western blotting analysis with a monoclonal 1 C 2 antibody that recognizes specifically pathological polyglutamine tracts. This disease is caused by an abnormal CAG/CAA expansion in the TATA-binding protein gene (TBP), a general transcription initiation factor. This abnormal expansion of glutamine tracts in TBP ranges 47 to 55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain that carried 48 CAG repeats detected neuronal intranuclear inclusion bodies (NIIs) that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1 C 2 antibody. Most patients presented in the third decade with gait ataxia and dementia, progressing over several decades to include bradykinesia, dysmetria, dysdiadockokinesis, hyperreflexia and paucity of movement. No abnormal eye movements were present in any patient. This disease resembles the spinocerebellar ataxias including Dentato-rubal pallidoluysian atrophy (DRPLA) more closely than any other form of neurodegenerative disorder. Further study of this disease should provide important information for unraveling the molecular pathogenesis of neuronal cell degeneration as well as for the development of future therapeutic interventions.
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PMID:[SCA17, a novel polyglutamine disease caused by the expansion of polyglutamine tracts in TATA-binding protein]. 1223 15

Trinucleotide expansions in the gene for the TATA-binding protein (TBP) have recently been described in cerebellar ataxia associated with dementia, pyramidal tract and basal ganglia symptoms. Expansions above 45 repeat units are commonly considered pathological, causing SCA17. Here, we present a German kindred with four siblings affected by cerebellar ataxia, chorea and dementia. Molecular genetic analysis yielded an expanded SCA17 allele coding for 48 glutamine residues that was transmitted from the mother to all of her six children. Apparently, the expanded allele does not cosegregate with the disease phenotype since the mother and two of the siblings do not show any clinical abnormality. This appears to be the first description of non-penetrance in SCA17.
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PMID:Phenotypical variability of expanded alleles in the TATA-binding protein gene. Reduced penetrance in SCA17? 1257 45

Spinocerebellar ataxia (SCA) 17 is a dominant, progressive, neurodegenerative disorder. The disease is caused by a triplet repeat expansion mutation within TATA-binding protein (TBP). Ataxia, dementia, parkinsonism and dystonia are common features. We have previously shown in several pedigrees that SCA-2 and SCA-3 can cause both parkinsonism and typical Parkinson's disease in the absence of prominent ataxia; a finding which has been confirmed by others. Given these previous findings and the description of parkinsonism as a common feature of SCA-17 we examined this locus in a series of probands from families with 2 or more members affected with parkinsonism (n=51) and a group of sporadic parkinsonism patients (n=59). We did not find any repeat sizes in the pathogenic range. The repeats we observed ranged from 29 to 41 (mean 36.8; median 37). We conclude that SCA-17 repeat expansion mutations are not a common cause of familial parkinsonism.
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PMID:Mutation at the SCA17 locus is not a common cause of parkinsonism. 1285 30

An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.
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PMID:SCA17 caused by homozygous repeat expansion in TBP due to partial isodisomy 6. 1289 85

Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a "pure cerebellar" or "cerebello-olivary" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.
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PMID:Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). 1295 69

We report on the clinical manifestation of spinocerebellar ataxia 17 (SCA17) in 3 members of a German family, in whom the pathological repeat expansion in the TATA-binding protein gene ranged from 53 to 55 repeats (normal: 29-42). The main clinical features were focal dystonia as presenting sign, followed by cerebellar ataxia, and, in the later course of one case, dementia and marked spasticity with signs of cerebellar and cerebral atrophy on brain computed tomography (CT) scan. In conclusion, SCA17 mutations should be considered in the differential diagnosis of focal dystonia.
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PMID:Focal dystonia as a presenting sign of spinocerebellar ataxia 17. 1497 80

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.
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PMID:Mutation at the SCA17 locus is not a common cause of primary dystonia. 1550 3

Huntington disease-like 2 (HDL2) is an autosomal dominant disorder characterized by adult-onset, progressive motor abnormalities, psychiatric disturbances, and dementia ending in premature death. Clinically, it most closely resembles Huntington disease (HD), although a subset of affected individuals have parkinsonian features. Here, we systematically compare 5 HDL2 and 5 HD brains with the hypothesis that, reflecting the clinical presentation, the neuropathology of the 2 diseases would be similar. Gross and microscopic examination revealed prominent striatal neuron loss and astrocytic gliosis in a dorsal to ventral gradient in each disorder and cortical atrophy. Nuclear protein aggregates were as common in HDL2 as in HD, and the ultrastructural features of HDL2 and HD aggregates were similar. Electron microscopy also revealed degenerating neurons, some with evidence of autophagy, in both HDL2 and HD. Small ribonuclear foci, previously associated with potentially neurotoxic RNA transcripts in HDL2, rarely colocalized with protein aggregates in HDL2 brain, although the protein aggregates were stained by anti-TATA-box binding protein antibodies. Overall, the neuropathologic features of HDL2 and HD are very similar but not identical, suggesting that the pathogenetic mechanisms of the 2 diseases may partially overlap.
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PMID:A comparison of huntington disease and huntington disease-like 2 neuropathology. 1837 32

A Japanese woman developed gait disturbances at 25 years of age, and subsequently underwent gradual changes in her personality. By the age of 42, she showed clear signs of dementia and cerebellar ataxia, and displayed behavioral abnormalities, choreic movements and hyperreflexia. The findings of MRI not only showed cerebellar and cerebral atrophy, but also revealed putaminal rim hyperintensity on T2-weighted images. We identified a heterozygously expanded CAG/CAA repeat (45/36) within the TATA-binding protein gene, leading to a diagnosis of SCA17. These results show that a 45 CAG/CAA repeat is pathological, giving rise to early-onset SCA17.
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PMID:A small trinucleotide expansion in the TBP gene gives rise to a sporadic case of SCA17 with abnormal putaminal findings on MRI. 1907 47

A persistent mystery about the ataxias has been why mutations in genes--many of which are expressed widely in the brain--primarily cause ataxia, and not, for example, epilepsy or dementia. Why should a polyglutamine stretch in the TATA-binding protein (that is important in all cells) particularly disrupt cerebellar coordination? We propose that advances in the genetics of cerebellar ataxias suggest a rational hypothesis for how so many different genes lead to predominantly cerebellar defects. We argue that the unifying feature of many genes involved in cerebellar ataxias is their impact on the signaling protein ITPR1 (inositiol 1,4,5-triphosphate receptor type 1), that underlies coincidence detection in Purkinje cells and could play an important role in cerebellar coordination.
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PMID:Human ataxias: a genetic dissection of inositol triphosphate receptor (ITPR1)-dependent signaling. 2022 42


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