Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old man was admitted with gait disturbance and dysarthria. He showed right-side cerebellar ataxia. Computed tomography of brain showed left thalamic bleeding. Nine months later, he was admitted again because of seizure and consciousness disturbance. He had a history of diabetes mellitus and gout for five years, but no hypertension. On physical examination the lungs and heart were normal. On neurological examination, he showed stupor,pupils and eye position were normal. He showed right hemiparesis and urinary incontinence. The deep tendon reflexes were (+) at the upper limbs and (2+) at the right knee and ankle. Blood pressure was 162/88 mmHg and glucose was 275 mg/dl. Other laboratory data were normal. Brain CT showed hemorrhage of the left frontal lobe. The cystatin C level in cerebrospinal fluid was 68 ng/ml. Therefore we suspected cystatin C deposit amyloid angiopathy. In this case, thalamic hemorrhage was initially thought to be amyloid angiopathy. In cases of cerebral hemorrhage in the elderly without hypertension, we must be considered amyloid angiopathy.
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PMID:[A case of recurrent cerebral hemorrhage considered to be cerebral amyloid angiopathy by cerebrospinal fluid examination]. 143 57

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. One hundred and eighty four index patients with autosomal dominant cerebellar ataxia type I were screened for this mutation. We found expansion in 109 patients from 30 families of different geographical origins (15%) and in two isolated cases with no known family histories (2%). The SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14 repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable mutations, a strong negative correlation was observed between the age at onset and the size of the CAG repeat (r = -0.81). The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration. The CAG repeat was highly unstable during transmission with variations ranging from -8 to +12, and a mean increase of +2.2, but there was no significant difference according to the parental sex. This instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.
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PMID:Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families. 915 45

We report the isolation of 41 partial transcripts containing trinucleotide repeats (TNRs) (CAG/CCG or CAA) from human spinal cord using a polymerase chain reaction-based method. The sequence analysis and database search at the nucleic acid and protein level revealed several classes of TNR-containing partial transcripts (TNRPTs). The TNRPTs included 16 known genes and 10 contained or partially overlapped with 13 expressed sequence tags (ESTs), some of which are known to contain TNRs and others which have previously not been shown to contain these repeats (e.g., clone 54 with homology for the homeobox protein HOX-A5). A further 15 partial transcripts showed no homologies in the databases and therefore may be unique. The validity of this approach is supported by the detection of nervous system-specific genes (e.g., glial fibrillary acid protein) and genes known to show trinucleotide expansions in disease (e.g., AAD10 associated with spino cerebellar ataxia type 2). This method provides a simple approach for the isolation of TNRPTs, from which full-length transcripts can be obtained and the discovery of TNR-containing genes may be facilitated. TNRPTs can also be used to study quantitative gene expression at the transcriptional level, to construct TNR-enriched cDNA libraries, and to make larger contigs from ESTs.
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PMID:Isolation and characterization of trinucleotide repeat containing partial transcripts in human spinal cord. 1073 97

At least 13 loci responsible for autosomal dominant cerebellar ataxia (ADCA) have been identified. Spinocerebellar ataxia 1, 2, 3, 6 and 7 are caused by translated CAG repeat expansions. However, in France, >30% of ADCAs are not explained by the known genes. Recently, analysis of the TATA box-binding protein (TBP) gene, one of the transcription factors known to contain a CAG/CAA repeat, in patients with progressive cerebellar ataxia revealed one sporadic case with 63 repeats. We examined this gene in 162 index cases with ADCA. An expanded repeat with 46 repeat units was detected in a single index case from Belgium. In this family, two affected members and six unaffected, but at-risk, individuals carried expanded alleles. Interestingly, the expanded repeat was stable during transmission. The main clinical features in six patients were cerebellar ataxia, dementia and behavioural disturbances with onset in their fourth to sixth decade. The main neuropathological finding was severe neuronal loss and gliosis in the Purkinje cell layer. Immunohistochemical analysis showed neuronal intranuclear inclusions containing expanded polyglutamine, indicating that this disease shares several features with other polyglutamine diseases. This study demonstrates that CAG/CAA repeat expansion in the TBP gene causes ADCA with dementia and/or psychiatric manifestations.
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PMID:CAG repeat expansion in the TATA box-binding protein gene causes autosomal dominant cerebellar ataxia. 1157 Dec 12

We report a group of 252 patients with a Huntington's disease-like (HDL) phenotype, including 60 with typical Huntington's disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington's disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington's disease. Taking into account patients with typical Huntington's disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
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PMID:Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. 1280 14

Trinucleotide repeat (TNR) expansion in the gene for TATA binding protein (TBP) has recently been described as causal for spinocerebellar ataxia type 17. The normal number of repeats has been considered to be 42 or less. An intermediate range with reduced penetrance has been assumed to be 43-47 CAA/CAG repeats. We examined this gene in 30 patients with autosomal-dominant cerebellar ataxia (ADCA), 35 patients with sporadic ataxia, 11 patients with Huntington's disease (HD), 351 patients with idiopathic Parkinson's disease (PD), 105 patients with Alzheimer's disease (AD), and 291 controls with no history of neurodegenerative disease. Three patients (one with sporadic PD and two with AD) carrying more than 42 TNRs in the TBP gene were identified. This reveals that the phenotype associated with CAG/CAA expansion in the TBP gene may be heterogeneous.
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PMID:Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases. 1536 89

TATA binding protein (TBP) is a general transcription factor that plays an important role in initiation of transcription. In recent years evidence has emerged implicating TPB in the molecular mechanism of a number of neurodegenerative diseases. Wild type TBP in humans contains a long polyglutamine stretch ranging in size from 29 to 42. It has been found associated with aggregated proteins in several of the polyglutamine disorders. Expansion in the CAA/CAG composite repeat beyond 42 has been shown to cause a cerebellar ataxia, SCA17. The involvement of such an important housekeeping protein in the disease mechanism suggests a major impact on the functioning of cells. The question remains, does TBP contribute to these diseases through a loss of normal function, likely to be catastrophic to a cell, or the gain of an aberrant function? This review deals with the function of TBP in transcription and cell function. The distribution of the polyglutamine coding allele lengths in TBP of the normal population and in SCA17 is reviewed and an outline is given on the reported cases of SCA17. The role of TBP in other polyglutamine disorders will be addressed as well as its possible role in other neurodegenerative diseases.
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PMID:TATA-binding protein in neurodegenerative disease. 1591 58

The spinocerebellar ataxia type 17 (SCA17) is characterized by cerebellar ataxia, dementia, and involuntary movements, including chorea and dystonia. In addition, psychiatric symptoms, pyramidal signs, and rigidity are common. MRI shows variable atrophy of the cerebrum, brainstem, and cerebellum. The autosomal dominantly inherited progressive neurodegenerative disorder is caused by an expanded CAA/CAG repeat coding for glutamine. Alleles of the normal range carry 25 to 42 glutamine residues, disease causing alleles 43 to 63. Alleles with 43 to 48 glutamine codons may be associated with incomplete penetrance. The mean age of onset is about 30 years for individuals with full-penetrance alleles, but ranges from three to 55 years.
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PMID:Spinocerebellar ataxia type 17 is caused by mutations in the TATA-box binding protein. 1785 80

SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.
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PMID:Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients. 1793 76

Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like-4 is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene leading to an abnormal expansion of a polyglutamine stretch in the corresponding protein. Alleles with 43 and 44 repeats have been identified in sporadic cases and their pathogenicity remains uncertain. Furthermore, incomplete penetrance of pathological alleles with up to 49 repeats has been suggested. The imperfect nature of the repeat makes intergenerational instability extremely rare and de novo mutations are most likely the result of partial duplications. This is one of the rarer forms of autosomal dominant cerebellar ataxia but the associated phenotype is often severe, involving various systems (cerebral cortex, striatum, and cerebellum), with extremely variable age at onset (range: 3-75 years) and clinical presentation. This gene is thought to account for a small proportion of patients with a Huntington's disease-like phenotype and cerebellar signs. Parkinson's disease-like, Creutzfeldt-Jakob disease-like and Alzheimer disease-like phenotypes have also been described with small SCA17 expansions. The abnormal protein is expressed at the same level as its normal counterpart and forms neuronal intranuclear inclusions containing other proteins involved in protein folding or degradation. The increase in the size of the glutamine stretch enhances transcription in vitro, probably leading to transcription deregulation. Interestingly, the TBP protein mutated in SCA17 is recruited in the inclusions of other polyglutaminopathies, suggesting its involvement in the transcription down-regulation observed in these diseases.
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PMID:Spinocerebellar ataxia 17 (SCA17) and Huntington's disease-like 4 (HDL4). 1841 87


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