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

From the linkage study of D6S89, we previously reported that hereditary OPCA in Japan is genetically heterogenous. Two pedigrees, P2 and P35, reported in this report, were not linked to D6S89. In order to examine possible correlation between OPCA genotypes and disease phenotypes, we studied clinically eight cases in these two pedigrees. One autopsied case in pedigree P2 was proven to have marked neuronal degeneration in the inferior olivary nuclei, pontine nuclei, cerebellar cortex, and substantia nigra. Dentate nucleus and oculomotor nuclei were free from neuronal degeneration. Clinical features of those 8 patients were fairly uniform, characterized by cerebellar ataxia, hypoactive DTR, and slow eye movement. Parkinsonism or choreiform movements were observed in one patient, respectively. Pupillary dilatation, twitching of face and tongue, limb amyotrophy were observed in patients of advanced stages. However, these signs were not dominating nor common throughout clinical course. None of our cases showed hyperactive DTR, limb spasticity, or external ophthalmoparesis. On the other hand, these latter signs were popular in SCA1 so far as reviewing the literature. The present study showed that there was possible correlation between genotypes and phenotypes in hereditary OPCA.
 ...
PMID:[Clinical study of gene locus heterogeneity in hereditary olivopontocerebellar atrophy (OPCA)--report of 2 pedigrees affected with non SCA1 type OPCA]. 181 83

We report on a Spanish family with cooccurrence of manic-depression and a form of hereditary cerebellar ataxia. All affected individuals in the second generation showed cerebellar ataxia and manic-depression simultaneously. Since anticipation has been described in both disorders and the pattern of segregation may be autosomal as well as X-linked, we have searched for a possible involvement of two candidate genes which are located either on an autosome (SCA1) or on the X-chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1 gene cannot be considered as a disease-causing mutation, and this gene should be initially discarded.
 ...
PMID:Familial cosegregation of manic-depressive illness and a form of hereditary cerebellar ataxia. 757 72

We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated with retinal degeneration and anticipation. Common clinical signs in this family include ataxia, dysarthria and severely impaired vision with the phenotype ADCA type II. Different subtypes of ADCA have proven difficult to classify clinically due to extensive phenotypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also genetically. During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been identified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q), SCA4 (16q), and finally SCA5 (11). We performed a genome-wide search of the Swedish ADCA type II family using a total of 270 microsatellite markers. Positive lod scores were obtained with a number of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.
 ...
PMID:Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1. 758 86

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA.
 ...
PMID:Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA. 761 90

Familial periodic cerebellar ataxia (FPCA) is a heterogeneous group of rare autosomal dominant disorders characterized by episodic cerebellar disturbance. A potassium-channel gene (KCNA1) has been found to be responsible for one of its subgroups, familial periodic cerebellar ataxia with myokymia (FPCA/+M; MIM 160120). A different subgroup that is not associated with myokymia (FPCA/-M; MIM 108500) was recently mapped to chromosome 19p. Here we have performed linkage analysis in two large families with FPCA/-M that also demonstrated neurodegenerative pathology of the cerebellum. Three markers in 19p13 gave significant lod scores (> 3.0), while linkage to KCNA1 and three known loci for spinocerebellar ataxia (SCA1, SCA2, and SCA3) was excluded. The highest lod score was obtained with the marker D19S413 (4.4 at recombination fraction 0), and identification of meiotic recombinants in affected individuals placed the locus between the flanking markers D19S406 and D19S226, narrowing the interval to 19 cM. A CAG trinucleotide-repeat expansion was detected in one family but did not cosegregate with the disease.
 ...
PMID:Familial periodic cerebellar ataxia without myokymia maps to a 19-cM region on 19p13. 776 67

A yeast artificial chromosome (YAC) contig located in 6p23 and spanning roughly 2.5 Mb has been constructed from the content of 10 sequence tagged sites (STSs) for YAC clones in 66 yeast colonies. Nine of the STSs have been genetically mapped in CEPH families. The order of STSs mapped with the contig is consistent with that of the genetic map. The order of loci that did not recombine with each other on the genetic map was inferred from the contig. Various regions of the contig are covered by multiple YAC clones that complement observed STS deletions. The STS for the CAG repeat sequence contained in the gene for spinal cerebellar ataxia 1 (gene symbol SCA1) is localized in the contig. It is likely that this gene is located in 6p23. The frequency of chimeric YAC clones in this contig is 35%. Eleven yeast colonies were found to carry two or more YACs. YAC subclones from some of these colonies showed size variation, and for several subclones, evidence consistent with deletion of a sequence tagged site.
 ...
PMID:A YAC contig in 6p23 based on sequence tagged sites. 780 26

This study addresses the question whether the different forms of autosomal dominant cerebellar ataxia (ADCA) are related to different ethnic/geographical regions in Europe. One mutation in families originating from Holland, Prussia and Italy has previously been localized to chromosome 6p (SCA1 locus), whereas the mutation in families of Iberic origin has been excluded from chromosome 6p. In a Danish five-generation pedigree with ADCA and in which previous HLA-serotyping had shown inconclusive linkage results, the present study shows unequivocal exclusion from the SCA1 locus, firstly through the use of the new, highly informative microsatellites D6S89 and D6S109, which closely flank the SCA1 locus, and secondly through the manifestation of disease in four pedigree members previously scored as unaffected. Additional molecular genetic analysis of the HLA DRbeta and F13A polymorphisms also argue against a cluster of ADCA genes on chromosome 6p. Since this study demonstrates the existence of non-SCA1 families and therefore heterogeneity in the North-European population, molecular family counselling remains restricted to the few known SCA1 families.
 ...
PMID:Molecular heterogeneity of autosomal dominant cerebellar ataxia: analysis of flanking microsatellites of the spinocerebellar ataxia 1 locus in a northern European family unequivocally demonstrates non-linkage. 809 59

Autosomal dominant cerebellar ataxia type 1 (ADCA1) is a clinical and genetic heterogeneous neurodegenerative disorder which leads to progressive cerebellar ataxia. One defective gene responsible for the disease was first localised to 6p (SCA1, spinocerebellar ataxia type 1) and the mutation has been more recently characterised. We have analysed the CAG-repeat mutation responsible for the SCA1 phenotype in a large Spanish kindred with 41 affected members, in which positive linkage with D6S89 was previously shown. All (10) clinically affected members analysed were heterozygous with one disease allele being between 41 to 57 CAG repeats, and the other in the normal range, from 6 to 39 repeats. Nine clinically unaffected individuals who were between the ages of 18 and 40, were found to have expansions of the CAG repeat (41 to 59), and 22 other 'at risk' individuals were found to have inherited the SCA1 gene with copies of the CAG repeat in the normal range. We have also observed that affected fathers passed on the mutated SCA1 gene with larger increases in the number of CAG repeats than affected mothers did. In one case a decrease in the number of CAG repeats (51 to 50) was detected in the transmission from the affected mother, and in two cases no change was observed in the transmission of a 41 allele repeat by a mother. As in the other disorders in which knowledge of the mutation has been obtained, analysis of the repeat expansion dramatically changes diagnosis of SCA1.
 ...
PMID:Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias. 811 82

The autosomal dominant cerebellar ataxias have proved particularly difficult to classify due to the lack of phenotypic concordance both within and between families. Genetic heterogeneity has been established, and disease loci for spinal cerebellar ataxia have been assigned to chromosomes 6 (SCA1), 12 (SCA2) and 14 (Machado Joseph disease (MJD)). Genetic analysis performed on a large Thai kindred with autosomal dominant cerebellar ataxia, in which frontal lobe signs and dementia are commonly observed in affected family members, exclude linkage to the SCA1, SCA2 and MJD loci. This demonstrates that mutation in at least one further locus can cause spinal cerebellar ataxia, indicating the need for caution in the use of markers for predictive testing or prenatal diagnosis these disorders.
 ...
PMID:Autosomal dominant cerebellar ataxia with dementia: evidence for a fourth disease locus. 816 21

The gene for one form of autosomal dominant spinal cerebellar ataxia (SCA1), is mapped by linkage to chromosome 6p, very close to the microsatellite locus D6S89. Eight large Italian kindreds segregating SCA1, as defined by very close linkage to D6S89, were genotyped with five microsatellite markers linked closely to D6S89, all mapping within a 6 cM interval on 6p. Multipoint linkage analysis and haplotypes from recombinants map SCA1 between two of these markers, D6S274 and D6S259, 5-6 cM apart. A single rare four marker haplotype within this interval shows linkage disequilibrium with the disease locus in southern Italy and is transmitted with SCA1 in five kindreds originating from this area.
 ...
PMID:The gene for spinal cerebellar ataxia 1 (SCA1) is flanked by two closely linked highly polymorphic microsatellite loci. 824 61


1 2 3 4 5 6 7 8 Next >>