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 49-year-old male was admitted to our hospital because of severe headache and dizziness which had occurred suddenly one day before admission. There was no past history contributory to cerebral hemorrhage but was family history of cerebrovascular accidents in his father and brother. Neurological examination revealed left homonymous hemianopsia, mild left hemiparesis, and left side hemi-neglect in simultaneous stimuli on bilateral extremities. Laboratory data including peripheral blood cells, coagulation tests, and serum chemistry were unremarkable. Brain CT and MRI demonstrated large lobar hematoma in the right parieto-occipito-temporal region. Cystatin C level in the CSF samples taken on the 39th and 59 th days (38 and 27 ng/ml respectively) were low, compared with the normal value (greater than 100 ng/ml). These findings suggest that the lobar cerebral hemorrhage of the present case might have been caused by cerebral amyloid angiopathy with cystatin C deposits.
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PMID:[A case of lobar cerebral hemorrhage with low concentration of CSF cystatin C]. 191 34

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of beta-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma. The disease is due to a point mutation at codon 693 of the amyloid precursor protein (beta PP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke. The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article.
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PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I--A review of clinical, radiologic and genetic aspects. 873 26

Hereditary Cystatin-C Amyloidosis (HCCA) is a genetic disorder in Icelandic families in which a defective cystatin-C amyloid protein is deposited in the walls of small and middle sized arteries. Cerebral vessels are most affected, resulting in recurrent cerebral hemorrhages and infarctions, usually with onset of clinical symptoms in the twenties or thirties and a rapidly deteriorating clinical course. The disease can be diagnosed by a skin biopsy in symptomatic patients. We report two patients (father and daughter) who did not have a known family history of the disorder and presented late in life with a progressive dementia, associated with cerebral hemorrhages in the younger patient. Cerebral MRI and CT scans of this patient showed extensive leukoencephalopathic changes. Brain tissue samples from both patients showed immunohistochemical reaction to cystatin-C in small and medium-sized cerebral arteries and extensive cortical and white matter microinfarctions. The amyloid changes were less severe in the older patient and a colocation of beta-amyloid protein and cystatin-C was observed in addition to neurofibrillary tangles and senile plaques. Subcortical and cortical infarctions were also observed. HCCA may present late in life with progressive dementia as the only clinical manifestation, reflecting a multi-infarct syndrome secondary to the amyloidosis. A coexpression of cystatin-C and beta protein may occur as in other cerebral amyloid disorders, probably as age-specific changes.
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PMID:Progressive dementia and leucoencephalopathy as the initial presentation of late onset hereditary cystatin-C amyloidosis. Clinicopathological presentation of two cases. 886 34

The authors describe an Italian family with autosomal dominant ataxia, dementia, psychiatric and extrapyramidal features, epilepsy, mild sensorimotor axonal neuropathy, and MRI findings of cerebral and cerebellar atrophy. A child had a distinctive presentation with onset at 3 years, growth retardation, fast progression, and early death. Molecular analysis demonstrated an expanded CAG/CAA repeat in the TBP gene (SCA-17). The repeat size was 66 triplets in the child and 53 in all the other patients.
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PMID:Intergenerational instability and marked anticipation in SCA-17. 1463 75

A family from the south of Western Australia is described with Dutch cerebral amyloid angiopathy (HCHWA-D). The proband died at age 60 from recurrent lobar haemorrhages in the brain, as did his sister and five other family members. The APP 693 mutation at position 22 of the Abetapeptide resulting in a glutamine for glutamic acid was identified in the proband and the affected sister. Pathologically lobar haemorrhages were found with cerebrovascular angiopathy; neuritic plaques were found but no neurofibrilary tangles. There was a leukoencephalopathy on MRI scanning. Dementia and cognitive decline has not been observed in this family. This is the first family reported outside of Europe and the Northern Hemisphere. The discovery highlights the importance of detecting this rare cause of fatal cerebral haemorrhage as it has implications for gene testing and general medical management.
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PMID:A Western Australian kindred with Dutch cerebral amyloid angiopathy. 1621 28

Cerebral amyloid angiopathy (CAA) is characterized by deposition of cerebrovascular amyloid protein in the media of leptomeningeal vessels. (amyloid B protein, cystatin C, transthyretin, gelsolin, and prion protein). It is a cause of cerebrovascular disorders including cerebral hemorrhage, cognitive impairment and unusually transient neurological symptoms. It is the main contributing factor to cerebral hemorrhage after hypertension in the elderly. We aimed to review epidemiological, pathophysiological and clinical and MRI imaging data in CAA.
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PMID:[Cerebral amyloid angiopathy]. 1730 82

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

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 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.
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PMID:Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism. 1908 10


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