Gene/Protein Disease Symptom Drug Enzyme Compound
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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Various cellular defects have been found in ataxia telangiectasia (A-T) cells including increased radiosensitivity, increased sensitivity to various chemical agents, a probable DNA repair defect and a defect in DNA synthesis. How these different features are related to each other is at present unknown. It has been suggested that there is a defect in A-T that acts in tissue differentiation as well as during growth and in the mature adult. This hypothesis is supported by the observations, for example, of an immature thymus present in patients, the production of alpha-fetoprotein, which results in a high serum level, and ovarian dysgenesis. A gene for A-T has recently been localized to chromosome region 11q22-23, a site involved in chromosomes translocations in some non-lymphoid leukaemias. At the chromosomal level the spontaneous abnormalities in A-T include, first, an increased frequency of cells showing chromosome translocations involving immune system genes that normally undergo rearrangement to form a functional product; secondly, the formation of telometric dicentrics in both lymphocytes and fibroblasts; and thirdly formation of long-lived chromosome damage following exposure to ionizing radiation and radiomimetic drugs. The gene defect underlying this disorder is unknown and distinguishing between primary and secondary effects of the mutant gene is difficult. We consider alternative models for retention of translocation T cells. First, it is possible that there is a defect in recognition of site-specific damage leading to retention of translocation cells that might otherwise be removed. Secondly, a feature common to the production of illegitimate T-cell receptor gene rearrangements and to formation of telomeric dicentric chromosomes in A-T cells is an increased period of time available for chromosome interchange, possibly due to a site-specific defect in strand break repair. It is possible that this defect may also prevent chromosome restitution following exposure of cells to ionizing radiation.
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PMID:Increased radiosensitivity and the basic defect in ataxia telangiectasia. 257 63

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

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a "bird-like" face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.
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PMID:Further delineation of the Nijmegen breakage syndrome. 278 40

We studied a case of familial ataxia-telangiectasia in a 15-year-old girl who had a clinical history of cerebellar ataxia and recurrent pulmonary infections. She was found at autopsy to have a hepatocellular carcinoma, which has been described twice previously in the literature as occurring with this disorder. Family studies on the majority of her seven siblings (the product of one father and two mothers who were identical twins) showed one brother to have classic features of cerebellar ataxia, IgA deficiency, markedly elevated alpha-fetoprotein levels, and characteristic chromosomal abnormalities. This boy also died later of hepatocellular carcinoma in 1984. An affected sister had previously died of a respiratory tract infection.
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PMID:Ataxia telangiectasia with hepatocellular carcinoma in a 15-year-old girl and studies of her kindred. 299 58

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

The role of altered developmental timing or heterochrony in morphologic evolution has intrigued classical and modern biologists. Analogous manifestations of developmental asynchrony occur in human dysmorphogenesis where they illustrate the residue and repertoire of phylogenetic change. Certain single malformations such as holoprosencephaly immediately suggest heterochrony by their resemblance to antecedent phylogenetic or embryologic structures. Multiple malformation syndromes of genetic, chromosomal, or teratogenic etiology may have altered developmental timing as an underlying theme. The persisting alpha-fetoprotein synthesis in ataxia-telangiectasia, the morphologic atavisms in Down or trisomy 13 syndromes, and the delayed growth or fetal to adult hemoglobin switch in diabetic embryopathy all exemplify developmental asynchrony. The perspective of heterochrony stresses the molecular history and hierarchy which is recapitulated with each pregnancy, and reconciles apparent discrepancies between the rates of molecular and morphologic evolution. Recognition of heterochrony places isolated anomalies in the context of pattern and suggests monitoring of teratogenesis through altered expression of ontogenetically regulated, phylogenetically relevant molecules.
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PMID:Heterochrony and human malformation. 328 59

The cases of identical twins with ataxia telangiectasia, early intellectual impairment and progressive spasticity are reported. Immunological tests revealed reduced levels of serum and salivary IgA, increased B cells, reduced T cells and raised alpha-fetoprotein. CT scan performed in one of the twins was normal. The pathogenesis of the spasticity is discussed.
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PMID:Ataxia telangiectasia in identical twins: unusual features. 377 10

Ataxia-telangiectasia (AT) is a genetic disorder of unknown pathogenesis, with primary effects on the immune and nervous systems. The presence of a fetal-like thymus and elevated alpha-fetoprotein (alpha FP) levels in patients with AT suggests that suppressed mesodermal development may be a factor in the development of this disease. We investigated this hypothesis by using electrophoretic and quantitative analyses to test for the presence of other fetal proteins in mesodermal tissues. With the exceptions of alpha FP and carcinoembryonic antigen, all other proteins assessed in these patients were present at levels or in isozymic patterns characteristic of a normal, nonfetal state.
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PMID:Fetal proteins in ataxia-telangiectasia. 618 Jan 90

Because of unconfirmed reports that the serum level of alpha-fetoprotein (AFP) is high in children with cystic fibrosis and intermediate in their siblings and parents, this level was measured in 25 children with cystic fibrosis, 26 of their siblings, 42 of their parents and 31 age-matched children without cystic fibrosis who were attending outpatient clinics of the Montreal Children's Hospital. Liver function tests were performed at the same time since patients with liver disease may have unusually high serum AFP levels and patients with cystic fibrosis often have liver involvement. AFP was not detected in any of the serum samples, and the results of the liver function tests were normal in all but 1 individual, a control subject. In simultaneous assays of serum from children with ataxia telangiectasia, however, high AFP levels were detected in 15 of 16 samples. Thus, measurement of the serum AFP level is of no value in detecting carriers of the cystic fibrosis gene.
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PMID:alpha-Fetoprotein and cystic fibrosis. 618 Aug 58


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