Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy.
 ...
PMID:Relative frequencies of CAG expansions in spinocerebellar ataxia and dentatorubropallidoluysian atrophy in 116 Italian families. 1089 92

Autosomal-dominant cerebellar ataxias (ADCA) may present as progressive or paroxysmal disorders. While the progressive ataxias have been named spinocerebellar ataxias (SCA), the paroxysmal disorders are designated episodic ataxias (EA). Until now, three different mutational mechanisms resulting in distinctive pathogenesis have been identified. The first type of mutation present in SCA1, SCA2, SCA3, and SCA7 is an expanded CAG repeat in genes of unknown function that are translated into proteins with expanded polyglutamine tracts. A common ultrastructural feature of these disorders is the formation of neuronal intranuclear inclusions (NII) harboring the expanded disease proteins and a variety of other proteins. The pathogenic role of these inclusions has yet to be clarified. A second group of disorders is the result of mutations in genes that code for ion channels. In EA-1, a disorder characterized by episodes of ataxia provoked by movement and startle, missense mutations in a potassium channel gene, KCNA1, have been found. Patients with EA-2, another form of paroxysmal ataxia, carry nonsense mutations of the gene encoding the alpha1A voltage-dependent calcium channel subunit, CACNA1A, that are predicted to result in truncated channel proteins. In SCA6, a progressive ataxia, an expanded CAG repeat in the 3' translated region of the CACNA1A gene, has been found. The third type of mutation is an untranslated CTG expansion resembling the mutation found in myotonic dystrophy. It is associated with a progressive ataxia, SCA8.
 ...
PMID:The molecular biology of the autosomal-dominant cerebellar ataxias. 1092 70

Dominantly inherited, late-onset pure cerebellar ataxia is a group of genetically heterogeneous neurodegenerative disorders. Approximately half of these disorders in the Japanese population are caused by moderate expansion of a CAG repeat in the coding region of the CACNA1A gene on chromosome 19p13 (SCA6). However, neither the loci nor the specific mutations for the remaining disorders have been determined. We performed systematic linkage analysis in a three-generation Japanese family with a locus or mutation that differed from those of known spinocerebellar ataxias. The family members with a late onset (> or =39 years old) exhibited pure cerebellar ataxia, whereas those with an early onset (< or =27 years old) first showed intermittent axial myoclonus followed by ataxia. Other neurological signs were sparse, and neuroimaging studies revealed that atrophy was confined to the cerebellum. Multipoint analysis and haplotype reconstruction ultimately traced this novel spinocerebellar ataxia locus (SCA14) to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter (Zmax = 4.08, corrected for age-dependent penetrance).
 ...
PMID:A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. 1093 65

To identify various subtypes of spinocerebellar ataxias (SCAs) among 57 unrelated individuals clinically diagnosed as ataxia patients we analysed the SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci for expansion of CAG repeats. We detected CAG repeat expansion in 6 patients (10.5%) at the SCA1 locus. Ten of the 57 patients (17.5%) had CAG repeat expansion at the SCA2 locus, while four had CAG expansion at the SCA3/MJD locus (7%). At the SCA6 locus there was a single patient (1.8%) with 21 CAG repeats. We have not detected any patient with expansion in the SCA7 and DRPLA loci. To test whether the frequencies of the large normal alleles in SCA1, SCA2 and SCA6 loci can reflect some light on prevalence of the subtypes of SCAs we studied the CAG repeat variation in these loci in nine ethnic sub-populations of eastern India from which the patients originated. We report here that the frequency of large normal alleles (>31 CAG repeats) in SCA1 locus to be 0.211 of 394 chromosomes studied. We also report that the frequency of large normal alleles (>22 CAG repeats) at the SCA2 locus is 0.038 while at the SCA6 locus frequency of large normal alleles (>13 repeats) is 0.032. We discussed our data in light of the distribution of normal alleles and prevalence of SCAs in the Japanese and white populations.
 ...
PMID:Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2 and SCA6 loci in nine ethnic populations of eastern India. 1094 7

Since the discovery of the first mutations that cause hereditary ataxias in the early 1990s, there has been continuous progress in deciphering the molecular pathogenesis of degenerative ataxias. Recent research in Friedreich's ataxia, the most frequent recessive ataxia, has provided further evidence that the clinical phenotype of this disorder is caused by abnormal oxidative phosphorylation due to mitochondrial dysfunction. The dominantly inherited spinocerebellar ataxias (SCAs) are genetically heterogeneous. Up to now, 11 distinct loci have been identified. The mutations that cause SCA1, SCA2, SCA3, SCA6 and SCA7 share the common feature of an expanded CAG sequence, encoding an abnormally long polyglutamine tract within the respective gene products. Recent pathogenetic research points to the importance of abnormal protein-protein interaction and altered gene transcription. The aetiology of many sporadic ataxias remains obscure. In some patients, association of ataxia with specific serum antibodies (antigliadin, antiglutamic acid decarboxylase) suggests an immune pathogenesis.
 ...
PMID:Recent advances in degenerative ataxias. 1097 64

Autosomal dominant cerebeller ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders that differ in both the clinical manifestations and modes of inheritance. At present, eight different genes causing ADCAs have been found: spinocerebeller ataxia type 1 (SCA1), SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubropallidoluysian atrophy (DRPLA). The relative prevalence of each mutation varies according to race and native place. We studied 117 unrelated ADCA families that originated from the Tohoku District in the northernmost part of Honshu Island in Japan (mainly Miyagi Prefecture in the central part of Tohoku District). The SCA1 mutation was the most frequent among the known disorders (24.8% of all such families). The relative prevalence of SCA1 in the Tohoku District is very high compared with the values already reported from other regions in the world. Because the population of this area had seldom moved, the alleles with SCA1 mutations (including alleles with an intermediate CAG repeat number) are assumed to have been present in this area for a long time.
 ...
PMID:High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan. 1101 7

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.
 ...
PMID:Genetic background of apparently idiopathic sporadic cerebellar ataxia. 1103 Apr 10

Because the transverse pontine fibres degenerate in some subtypes of spinocerebellar degeneration (SCD), demonstration of these fibres may be helpful for radiological diagnosis of SCD. Using multishot diffusion-weighted MRI, we attempted to find a way to show the transverse pontine fibres. We assessed the quality of demonstration of these fibres on DWI and of abnormal high signal in the pons and middle cerebellar peduncles on T2-weighted images. We examined evaluated 24 control subjects and 12 patients with SCD: two with sporadic olivopontocerebellar atrophy (OPCA), five with spinocerebellar ataxia type 1 (SCA1), two with SCA3, and three with SCA6. In all control subjects and patients with SCA6, we succeeded in demonstrating the transverse pontine fibres as clear low-signal bundles using DWI. In two patients with SCA3, these fibres were identified less distinctly. In contrast, in two patients with sporadic OPCA and in four of five patients with SCA1, the fibres were not identified. In both patients with sporadic OPCA, abnormal high-signal foci were seen in the base of the pons and middle cerebellar peduncles on T2-weighted images; no such foci were detected in any patient with SCA1, SCA3 or SCA6. DWI seems to be useful for demonstrating transverse pontine fibres. Abnormal high signal in the pons and middle cerebellar peduncles may provide a clue to differentiation of sporadic OPCA from other types of SCD.
 ...
PMID:Diffusion- and T2-weighted MRI of the transverse pontine fibres in spinocerebellar degeneration. 1115 84

The objective of this study was to investigate cerebellar metabolism in patients with autosomal dominant cerebellar ataxia type 1 (ADCA-I) carrying two distinct mutations of spinocerebellar ataxia (SCA). Non-invasive image-guided proton magnetic resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation. For MRSI, we employed a spin-echo sequence (TR = 1500 msec, TE = 135 msec, slice thickness = 15 mm, FOV = 240 mm) and a stimulated-echo sequence (TR = 1500 msec, TE = 20 msec, slice thickness = 15 mm, FOV = 240 mm). Measures included the peak integral ratios of neuronal and glial markers [N-acetylaspartate (NA) to creatine (Cr), choline-containing compounds (CHO) to Cr, and lactate (LAC) to Cr]. We found NA:Cr ratios were significantly lower in patients with SCA2 (40.4% lower) compared to patients carrying the SCA6 mutation. CHO:Cr ratios differed between the two mutations using short echo time (30.8% lower in SCA2), but not when applying long echo time 1H-MRSI. Measurements using long echo time revealed LAC peaks in all SCA2 patients. 1H-MRSI revealed metabolic differences between SCA2 and SCA6 patients. NA:Cr ratios were significantly lower in patients with the SCA2 mutation compared to the SCA6 mutation, and LAC signals were obtained in the cerebella of SCA2 patients. In addition, CHO:Cr ratios showed different behavior using short and long TE, indicating differences in relaxation times of choline compounds in SCA2.
 ...
PMID:Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6. 1127 99

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. CAG repeat expansions in the causative genes have been identified as the basic cause of several types of SCAs, and have been used for the diagnoses and classifications of patients with ataxia. In order to assess the frequency and CAG repeat size ranges of SCAs, and to establish an effective strategy for molecular diagnosis, we performed a molecular analysis of SCA1, SCA2, SCA3, SCA6, and SCA7 in 76 patients. These patients were as follows: 32 with dominant inheritance, 39 sporadic cases, and 5 with unknown family histories. The normal and affected CAG repeat size ranges were established at five SCA loci in Koreans, which was consistent with previous reports. The total prevalence of the five types of SCAs was 39.5% in the 76 patients with ataxia, regardless of their family history. It was 75.0% in the 32 families with a dominant inheritance. The most frequent type was SCA3 (15.8%), followed by SCA2 (14.5%). Both types combined formed 76.7% of the 30 patients with CAG expansions. SCA1, SCA6, and SCA7 were less frequent, affecting 3.9%, 2.6%, and 2.6% of the cases, respectively. This mutation spectrum is quite different from a previous report concerning Koreans, but is similar to the distributions that are seen in several ethnic populations worldwide. For a correct and effective diagnosis of SCAs, we suggest that a molecular diagnosis be undertaken, even in patients without a family history, as well as those with a family history. A stepwise approach is also recommended. Patients with ataxia should be tested for SCA2 and SCA3. Individuals testing negative should be tested for SCA1, SCA6, and SCA7.
 ...
PMID:Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. 1180 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>