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)

13 children with ataxia-telangiectasia were followed for 6 years. Unlike previously reported cases, these patients had progressive, debilitating neurological disease and slight pulmonary or infectious symptoms. Immunological dysfunction was variable and endocrinological defects were absent. Oculomotor findings, alpha-fetoprotein levels, and the incidence of chromosomal breakage were the most consistent parameters in the diagnosis of the condition. This disease should be considered in any patient with chronic ataxia, regardless of immunological findings or whether he has a history of infections.
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PMID:Diagnostic considerations in ataxia-telangiectasia. 9 14

A second family is described with a combination of defective thymus-dependent immunity and cerebral palsy. The cerebral palsy comprised nonprogressive dysequilibrium and mild spastic diplegia without limb ataxia. This genetic entity of presumed autosomal recessive inheritance is clearly distinguished from ataxia-telangiectasia. Immunological abnormalities should be sought in other familial or unexplained cerebral palsy syndromes.
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PMID:Familial dysequilibrium-diplegia with T-lymphocyte deficiency. 108 13

Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.
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PMID:Ataxia-telangiectasia: some historic, clinical and pathologic observations. 109 82

It has been found that irradiation in doses 0.5-2.0 Gy does not enhance the frequency of sister chromatid exchanges in cells of patients with Down's syndrome and ataxia-telangiectasia compared to the normal cells. In the case of ataxia, this phenomenon was accompanied with radioresistant replicative DNA synthesis, whereas in two cases of Down's syndrome the replicative DNA synthesis was found to be as radiosensitive as in the norm. According to these data, the mechanism of sister chromatid exchanges proposed in our previous publication (Pleskach et al., 1988) seems to be rather doubtful.
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PMID:[The relationship between the radiosensitivity of DNA replicative synthesis and the formation of sister chromatid exchanges]. 183 42

A number of characteristics in the human genetic disorder ataxia-telangiectasia are compatible with an alteration to chromatin structure or the recognition of that structure by an enzyme or DNA binding protein. We describe here reduce activity of DNA topoisomerase type II in a number of Epstein Barr Virus-transformed ataxia-telangiectasia lymphoblastoid cell lines. Enzyme activity was reduced 10-fold or greater in 4 out of 5 cell lines compared to controls. In the remaining cell line approximately a 2-3 fold reduction was evident in partially purified extracts. DNA topoisomerase type I activity was found to be the same as controls in all the cell lines. Northern blot analysis revealed that the same level of DNA topoisomerase II mRNA was expressed in ataxia-telangiectasia and control cell lines. The size and amount of the enzyme did not differ appreciably from that observed in control cells. The reduced activity of DNA topoisomerase II in ataxia-telangiectasis cells might be explained by amino acid substitutions, small deletions in DNA or by a defect in post-translational modification in these cells.
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PMID:Defective DNA topoisomerase II in ataxia-telangiectasia cells. 196 59

This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. They have, in addition, microcephaly and mental retardation. Complementation studies were performed utilizing Sendai virus--mediated fusion of fibroblast cell lines. Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. These data suggest that the Nijmegen breakage syndrome and the patients described here are not genetically distinct entities but form a spectrum of one disorder.
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PMID:ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome. 249 Nov 81

Sixty-eight human fibroblast cell strains were assayed for radioresistant DNA synthesis (RDS), which is defined here as the absence of a steep component of inhibition of DNA synthesis in a dose-response curve when rate of DNA synthesis is plotted against radiation doses from 0 to 20 Gy or more. Twenty-seven strains from patients who were previously diagnosed to have ataxia-telangiectasia (AT) were positive for this feature. Among the cell strains that did not show RDS were two from AT obligate heterozygotes (i.e., the parents of AT patients), two from patients with Alzheimer disease, two from patients with Friedreich ataxia, one from a patient with Bloom syndrome, one from a patient with Down syndrome, and six from patients with various immunodeficiencies. Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients. RDS therefore is not a necessary trait of human genetic diseases that involve radiosensitivity or immunodeficiency. Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.
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PMID:Radioresistant DNA synthesis and human genetic diseases. 272 85

Two sisters, 11 and 9 years old respectively, had the clinical features of a progressive neurological disorder similar to the ataxia-telangiectasia (AT) syndrome. The two patients have ataxia and chromosome instability with rearrangements of chromosomes 7 and 14 but no telangiectasia, nor the range of immunological anomalies typical of AT. Comparison with similar cases from the literature leads to the conclusion that either there is a specific disorder characterized by ataxia-without-telangiectasia and with the same cytogenetic pattern of AT, or AT shows a wider variability of phenotypic expression than thought before.
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PMID:Ataxia-without-telangiectasia in two sisters with rearrangements of chromosomes 7 and 14. 322 96

We report 14 patients with a slowly progressive syndrome featuring ataxia, choreoathetosis, and ocular motor apraxia in both the horizontal and vertical planes. Although the neurological signs were indistinguishable from those of ataxia-telangiectasia, the onset tended to be later and none of the patients had evidence of multisystemic involvement. Specifically, there was no tendency to frequent infections, and immunoglobulins, alpha-fetoprotein, T- and B-lymphocyte markers, and chromosomes 7 and 14 were normal in all tested patients. The simultaneous absence of telangiectasias and of other nonneurological manifestations made ataxia-telangiectasia an unlikely diagnosis. We suggest that these patients suffer from an unusual type of spinocerebellar degeneration. This syndrome has been observed in different populations from three continents, with a genetic pattern suggesting recessive autosomal inheritance.
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PMID:Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. 323 52

Cells derived from individuals with the ataxia-telangiectasia syndrome demonstrate a number of unusual properties. They are highly sensitive to the lethal effects of ionizing radiation and also fail to demonstrate the normal inhibition of DNA synthesis associated with this type of DNA-damaging agent. Additionally, a number of ataxia-telangiectasia lymphoblastoid lines have been shown to have an unusual regulation of the cellular actin levels. However, the primary lesion causing ataxia-telangiectasia is unknown. In this paper we report an altered cellular morphology in three ataxia-telangiectasia fibroblast lines, but not in a number of control fibroblast lines. Investigation of the cytoskeleton using antibodies against certain cytoskeletal proteins revealed a difference in the microfilament pattern from ataxia-telangiectasia fibroblasts compared to controls. Ataxia fibroblasts showed a microfilament stress fiber pattern that appeared to have a more well defined and abundant array of stress fibers than control fibroblasts. In contrast, no differences were observed in the microtubule array, nor in the vinculin patterns between any of the cell lines. In addition to the differences in the microfilament patterns, ataxia-telangiectasia fibroblasts differed in their ability to recover from microfilament disruption by dimethyl sulfoxide. Control fibroblasts returned to a normal cellular state in a shorter time compared to ataxia fibroblasts, as judged by indirect immunofluorescence using antiactin. These results provide further evidence for a cytoskeletal anomaly in ataxia-telangiectasia.
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PMID:Altered cellular morphology and microfilament array in ataxia-telangiectasia fibroblasts. 391 Apr 38


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