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

Spinocerebellar ataxia type 1 (SCA1) is one form of autosomal dominant cerebellar ataxia (ADCA) caused by trinucleotide (CAG) repeat expansion within a mutant gene. We investigated 25 patients from 15 Russian ADCA families for SCA1 mutation and found an expanded CAG repeat in 5 families. Mutant chromosomes contained 41-51 CAG repeats (mean 46.1, SD 3.1), and normal chromosomes displayed 21-27 repeat units (mean 24.7, SD 1.3). Progressive cerebellar ataxia in our series of SCA1 patients was very commonly associated with dysarthria (in all cases) and pyramidal signs (in 10 of 11 cases). In three patients from one family we found optic atrophy, which has never been described before in genetically proven cases of SCA1. We observed no specific clinical features distinguishing SCA1 from non-SCA1 patients. In contrast to the high frequency of SCA1 in our series, we found no patients with Machado-Joseph disease, another form of ADCA caused by expanded CAG repeat.
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PMID:Spinocerebellar ataxia type 1 in Russia. 883 39

Sixty-five patients suffering from autosomal dominant cerebellar ataxia-I(ADCA-1) were subjected genotype phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, pale discs and dysphagia were more frequent in SCA1 compared SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCA1 were similar but less pronounced. In contrast, SCA3 patients had only mild cerebellar and brain stem atrophy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter of the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type I falls into an intermediate range that overlaps with both SCA2 and SCA3. However, the clinical syndrome observed in SCA1 patients is different from that in SCA2 and SCA3.
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PMID:Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. 893 75

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

Spinocerebellar ataxia type 6 (SCA6) is a newly classified autosomal-dominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCA6 mutation. Of these, 35 patients were found to have expanded CAG repeats in the SCA6 gene, indicating that second to SCA3, SCA6 is the most common ADCA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas normal alleles had seven to 17 repeats. There was no change in the CAG repeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCA6 was slowly progressive cerebellar ataxia; multisystem involvement was not common. The 35 patients included nine cases without apparent family history of cerebellar ataxia. The sporadic cases had smaller CAG repeats (21 or 22 repeats) and a later age at onset (64.9 +/- 4.9 years) than the other cases with established family history. We also identified one patient who was homozygous for the SCA6 repeat expansion. The homozygote showed an earlier age of onset and more severe clinical manifestations than her sister, a heterozygote carrying an expanded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an important role in phenotypic expression in SCA6.
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PMID:Spinocerebellar ataxia type 6. Molecular and clinical features of 35 Japanese patients including one homozygous for the CAG repeat expansion. 937 91

Spinocerebellar ataxia type 6 (SCA6) is the most recently identified mutation causing autosomal-dominant cerebellar ataxia without retinal degeneration (ADCA). The SCA6 mutation is allelic with episodic ataxia type 2 (EA-2), but the two differ clinically because of the presence of progressive, rather than episodic, ataxia in SCA6. SCA6 accounts for 12% of families with ADCA in an ethnically heterogeneous population of patients. Clinical examination, quantitative eye movement testing, and imaging data show that the brainstem is normal in most patients with SCA6, especially within the first 10 years of symptoms. Most patients show progressive ataxia from the onset, but several patients show an episodic course resembling EA-2. Thus, SCA6 mutations not only account for patients with ADCA I and ADCA III phenotypes but also for some patients presenting with episodic features that are typical for EA-2. Interestingly, a compound heterozygote for the SCA6 expansion manifested an earlier onset and more rapid course than family members with the same larger expanded allele.
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PMID:Spinocerebellar ataxia type 6. Frequency of the mutation and genotype-phenotype correlations. 937 91

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant cerebellar ataxia associated with small expansions of the trinucleotide repeat (CAG)n in the gene CACNL1A4 on chromosome 19p13, which encodes the alpha1 subunit of a P/Q-type voltage-gated calcium channel. We describe clinical, genetic, neuroimaging, neuropathological, and quantitative oculomotor studies in four kindreds with SCA6. We found strong genetic linkage of the disease to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles in two large ataxia kindreds. The expanded alleles were all of a single size (repeat number) within the two large kindreds, numbering 22 and 23 repeat units. It is noteworthy that the age of onset of ataxia ranged from 24 to 63 years among all affected individuals, despite the uniform repeat number. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of ocular motor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibulo-ocular reflex. These studies identify a distinct phenotype associated with this newly recognized form of dominant SCA.
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PMID:Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. 940 87

Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in the gene encoding the alpha1A-voltage-dependent-calcium channel subunit (CACNLIA4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prevalence of SCA6 in the Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA III. The specificity and stability of the CAG repeat were examined in additional individuals and families with other miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12 proband cases with ADCA III, but not in others. The CAG repeat was 21-33 in the disease-associated alleles (n=56), and 4-18 in normal alleles (n=1148). Expanded alleles were stable during transmission, and a significant inverse correlation for CAG repeat number with age at onset was noted. Our results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified.
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PMID:SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia. 955 93

Spinocerebellar ataxia type 6 (SCA6) is genetically defined as a group of SCA characterized by late-onset pure cerebellar ataxia clinically and by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNL1A4) on chromosome 19p13.1 genetically. We analyzed the initial symptoms and the mode of progression in this disorder on 25 genetically verified patients. The initial symptoms were recurrent episodes of transient vertigo (72%) or unsteady gait (28%). Neurologically, they showed apparent gaze-evoked nystagmus (92%), transient positional nystagmus (83%), and periodic alternating nystagmus (4%), in addition to cerebellar ataxia. In addition to these episodic symptoms, all patients developed progressive cerebellar ataxia over years. These fluctuating symptoms at the initial stage of the illness were clearly different from those of other SCA, rather overlapping with those of episodic ataxia type 2 (EA2), an allelic disorder of SCA6. The clinical similarity indicates that there might be a common mechanism at least in part causing these two disorders. The mode of progression and their neurological features were also presented.
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PMID:[Initial symptoms and mode of neurological progression in spinocerebellar ataxia type 6 (SCA6)]. 984 64

Spinocerebellar ataxia type 2 (SCA2) is an inherited neurodegenerative disorder characterized clinically by cerebellar ataxia, slow eye movement, hyporeflexia, involuntary movement, dementia and sensory disturbance and neuropathologically by neuronal loss, mainly in the cerebellar cortex involving all three layers, the pontine nucleus, the inferior olivary nucleus, anterior horn, substantia nigra and thalamus. For making one's diagnosis, it is necessary to give careful consideration to two factors, (age at onset, disease duration). A distinctive neuropathological feature is having both simple atrophy (without degeneration) and numerical atrophy. SCA2 is associated with an expanded CAG repeat that encodes polyglutamine of a gene and a larger number of the repeat is associated with earlier onset and more severe symptoms and more severe neuronal degenerations.
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PMID:[Correlation of clinichopathological features and CAG repeats in SCA2]. 1022 70

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by the trinucleotide(CAG) repeat expansion in the alpha1A-voltage-dependent calcium channel gene. In this paper, we describe clinical, neuropathological and genetic characteristics of SCA6. Clinical analysis on 82 affected individuals revealed that SCA6 is characterized by later-onset pure cerebellar syndrome. Phenomenon of anticipation was not obvious, demonstrating another characteristics of SCA6. Neuropathologically, SCA6 brains consistently showed predominant degeneration of the Purkinje cell. In contrast with other CAG repeat diseases, the ubiquitin-positive neuronal intranuclear inclusion was absent in SCA6. Molecular genetically, SCA6 was characterized by an expansion of a small and stable CAG repeat. We conclude that SCA6 has several unique features compared to other CAG repeat diseases.
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PMID:[Clinical, neuropathological and genetic characteristics of spinocerebellar ataxia type 6 (SCA6)]. 1022 83


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