Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant progressive neurodegenerative disorder characterized by ataxia, dysarthria, ophthalmoparesis, and variable degrees of amyotrophy and neuropathy. Symptoms usually develop in the third or fourth decade but anticipation has been noted in juvenile onset cases. Neuropathologic findings include severe neuronal loss in the cerebellum and brainstem as well as degeneration of spinocerebellar tracts. The SCA1 gene which maps to the short arm of human chromosome 6 was identified using a positional cloning approach. The disease causing mutation is an expansion of a CAG trinucleotide repeat which lies within the coding region of a novel protein, ataxin-1, and encodes a polyglutamine tract. The number of CAG repeats varies from 6-39 repeats on normal alleles and 40-81 repeats on SCA1 alleles. The repeat has a perfect CAG configuration on expanded alleles whereas it is interrupted by 1-3 CAT units on normal alleles. Both wild type and expanded alleles are transcribed, ruling out impairment of transcriptional efficiency in SCA1. A pathogenetic model is proposed based on the findings in SCA1 and other neurodegenerative diseases caused by expansion of polyglutamine tracts. The expanded polyglutamine tract in ataxin-1 may lead to neurodegeneration through a gain of function mechanism involving aberrant interactions with other molecules in the involved neurons.
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PMID:Spinocerebellar ataxia type 1. 761 95

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by ataxia, dysarthria and progressive bulbar dysfunction. The SCA 1 gene which maps to the short arm of chromosome 6 has been isolated using a positional cloning approach. The SCA1 transcript is 10660 bases and encodes a novel protein, ataxin-1, with a predicted molecular weight of 87 kDa. Expansion of a CAG repeat localized near the amino terminus of ataxin-1 has been found to be the mutational mechanism in SCA1. This CAG repeat is highly polymorphic with normal alleles containing 6-39 repeats. Individuals affected with SCA1 have one normal allele and one expanded allele containing 40-81 repeats. The size of the repeat correlates inversely with the age of onset of symptoms and the severity of disease. The repeat is a continuous CAG repeat tract on SCA1 chromosomes whereas in > or = 98% of normal alleles one or more CAT interruptions break the CAG repeat tracts into two tracts containing less than 18 repeats each. This suggests that loss of CAT interruptions within the SCA1 CAG repeat on normal chromosomes leads to triplet instability.
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PMID:Spinocerebellar ataxia type 1. 762 Jan 19

The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.
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PMID:Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. 948 73