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

The gene responsible for spinocerebellar ataxia type 1 (SCA1) has been localized to a 6.7-cM region between the centromeric marker D6S109 and the telomeric marker D6S89. We screened two yeast artificial chromosome (YAC) libraries using sequence-tagged sites at D6S89 and at newly identified markers in 6p22-p23. Fifty YAC clones were identified and 34 insert termini were isolated from some of these YACs for detailed overlap mapping and long-range restriction analysis. A large YAC contig estimated to span 2.5 Mb was developed and genetic analysis in five large SCA1 kindreds using highly informative dinucleotide repeat polymorphisms mapped to this contig allowed the identification of D6S274 as the closest centromeric flanking marker for SCA1. Long-range restriction analysis determined the size for the critical SCA1 region, as defined by the two flanking markers D6S274 and D6S89, to be 1.2 Mb. This region is spanned by a minimum set of four nonchimeric YAC clones. The development of a 2.5-Mb YAC contig in 6p22-p23 provides valuable reagents for characterization of this genomic region and for the cloning of the SCA1 gene.
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PMID:Mapping and cloning of the critical region for the spinocerebellar ataxia type 1 gene (SCA1) in a yeast artificial chromosome contig spanning 1.2 Mb. 830 72

SCA1 is a dominant spinocerebellar ataxia (SCA) and a multi-systemic syndrome caused by abnormal expansion of unstable CAG repeat in a novel gene located on chromosome 6p22-p23. We clinically studied 35 Japanese SCA1 patients who were assumed to have come from a common origin. The age at onset ranged from 15-63 years, and significantly correlated with CAG repeat units of mutant alleles. Ataxia was the initial symptom, and the majority of patients had a similar history of signs and symptoms. Nystagmus was at first minimal, later attenuated, and a slow saccade followed. Limb tendon reflexes were mostly hyperactive and depressed with the development of diffuse amyotrophy. The cardinal feature was ataxia-hyperreflexia-late slow saccade syndrome with terminal amyotrophy. Although the phenotype of SCA1 overlaps with those of other dominant SCAs, some facets of the neurological events differ from either SCA2 with ataxia-hyporeflexia-slow saccade syndrome, or early-onset Machado-Joseph disease with dystonia-bradykinesia-spasticity syndrome.
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PMID:Clinical features and natural history of spinocerebellar ataxia type 1. 882 76

The recent advances in gene analysis have greatly facilitated the classification of autosomal dominant spinocerebellar ataxia (SCA). Analyses of linkage in large families with SCA have assigned gene foci to at least 8 chromosomes. One gene is located in the short arm of chromosome 6 (6p22-p23) and causes spinocerebellar ataxia type 1 (SCA1). A gene in the long arm of chromosome 14 (14q24.3-q32) underlies Machado-Joseph disease (MJD). A third gene locus is assigned to the short arm of chromosome 12 (12p2-pter) causing dentatorubropallidoluysian atrophy (DRPLA). The gene for spinocerebellar ataxia type 2 (SCA2) is located in the 12q23-24. Subsequently, a sporadic counterpart of hereditary olivopontocerebellar atrophy of the Menzel type is clearly defined, and all the syndromes (non-hereditary olivopontocerebellar atrophy, striatonigral degeneration and Shy-Drager syndrome) are now lumped under the term of multiple system atrophy (MSA). Oligodendroglial cytoplasmic inclusions appear to be specific for and diagnostic of MSA. As the clinical features in SCA are variable and often appear to overlap with one another, which makes accurate classification difficult if not possible, the genotype is required for their unequivocal classification. However, major neuropathological features clearly distinguish SCA1 from SCA3/ MJD cases; the medial segment of the globus pallidus and intermediolateral column lesions in SCA3/MJD, and inferior olive and cerebellar cortical degeneration in SCA1. It has been stated that neurodegeneration in SCA3/MJD is more homogeneous than in SCA1 or SCA2 and that degeneration of the pallidoluysian system is not present in the latter. The pertinent pathology in each of the three types of SCA is illustrated. The background of clinicopathology and genetic analysis of dentatorubropallidoluysian atrophy is also reviewed.
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PMID:Clinicopathology of spinocerebellar degeneration: its correlation to the unstable CAG repeat of the affected gene. 905 87

Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.
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PMID:Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases. 2430 Jan 64

Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.
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PMID:Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2). 2666 62