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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular epidemiology may help fill the gap between epidemiological and biological models for cancerogenesis, allowing useful comparisons between series of cases carrying different biological characteristics. The defective regulation of immune responses is probably the common basis of cancer origin in genetically determined immune deficiency (GDID). Lymphomas are the most common neoplasms, showing an extremely high incidence in early age, frequent unusual location (extra-nodal) and histology, and rapid progression and spread with little response to therapy. A high incidence of lymphoma is also found in acquired (AIDS) or iatrogenic (transplant recipients) immune defective patients. The emergence of a malignant clone may be linked to unregulated polyclonal B- or T-cell proliferation and to disturbances in chromosomal rearrangements and in clonal selection, which are unique features of the immune cells regulation. It is useful to compare patterns of malignancies observed in GDIDs and in chromosomal breakage syndromes (CBS). In ataxia-teleangectasia (AT), selective errors at sites of special recombination involved in immune cell rearrangements may account for both immune deficiency and frequent types of malignant transformation. Different cytogenetic alterations and different types of malignancies are more common in Bloom syndrome, and in other GDIDs unrelated to chromosomal fragility, possibly due to different regulatory impairments. Viral infection (EBV, HPV, CMV) is likely to be a factor in any of the above steps. Therefore, individual exposure to viral (or other environmental) agents may be related to frequent location (skin, ano-genital areas, digestive tracts) of nonlymphatic cancers both in some GDIDs and in acquired or iatrogenic immune deficiencies. Cells that are homozygous for GDID are not malignant themselves, but are more likely to undergo new mutations to malignancy, due both to disregulation of the immune system and to environmental agents.
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PMID:Molecular epidemiology of cancer in immune deficiency. 203 52

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

In this paper, a survey is given of the immunological disturbances in some chromosome instability disorders (e.g. Bloom syndrome, ataxia teleangiectasia and Nijmegen Breakage syndrome). Further, the clinical symptoms and the diagnostic approach will be discussed.
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PMID:[Immunodeficiency and chromosome instability]. 320 18

There exist numerous genetic disorders, marked by chromosome instability, that are strikingly associated with various cancers. Both the chromosomal instabilities and neoplastic outcomes are related to abnormalities of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis. Among these diseases are ataxia telangectasia and Nijmegen breakage syndrome, with increased incidences of lymphomas. Bloom syndrome, Werner syndrome, and Rothmund-Thompson syndrome, each characterized by a DNA helicase defect, are associated with early incidences of different cancers. Other diseases combining the phenotype of chromosomal instabilities and neoplastic development are Fanconi anemia and breast cancers associated with mutant BRCA1 and BRCA2 genes. The cloning of the encoding genes and the characterization of their products have resulted in partial understanding of the pathways of cellular DNA surveillance and maintenance of genomic rectitude. The exact pathways fully linking the genetic defect mechanisms to the eventual development of various neoplasias remain to be elucidated, but progress in defining the molecular genetics of these entities suggests that many of them are disorders of DNA recombination. Each defect involves a separate protein in these complex pathways.
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PMID:Chromosome breakage syndromes and cancer. 1240 92

We review the genes and proteins related to the homologous recombinational repair (HRR) pathway that are implicated in cancer through either genetic disorders that predispose to cancer through chromosome instability or the occurrence of somatic mutations that contribute to carcinogenesis. Ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), and an ataxia-like disorder (ATLD), are chromosome instability disorders that are defective in the ataxia telangiectasia mutated (ATM), NBS, and Mre11 genes, respectively. These genes are critical in maintaining cellular resistance to ionizing radiation (IR), which kills largely by the production of double-strand breaks (DSBs). Bloom syndrome involves a defect in the BLM helicase, which seems to play a role in restarting DNA replication forks that are blocked at lesions, thereby promoting chromosome stability. The Werner syndrome gene (WRN) helicase, another member of the RecQ family like BLM, has very recently been found to help mediate homologous recombination. Fanconi anemia (FA) is a genetically complex chromosomal instability disorder involving seven or more genes, one of which is BRCA2. FA may be at least partially caused by the aberrant production of reactive oxidative species. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in HRR; BRCA2 associates with Rad51 and appears to regulate its activity. We discuss in detail the phenotypes of the various mutant cell lines and the signaling pathways mediated by the ATM kinase. ATM's phosphorylation targets can be grouped into oxidative stress-mediated transcriptional changes, cell cycle checkpoints, and recombinational repair. We present the DNA damage response pathways by using the DSB as the prototype lesion, whose incorrect repair can initiate and augment karyotypic abnormalities.
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PMID:Recombinational DNA repair and human disease. 1242 31

A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS approximately FA approximately XP>DS approximately AT approximately controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (< or =15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed.
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PMID:Different patterns of in vivo pro-oxidant states in a set of cancer- or aging-related genetic diseases. 1805 16

DNA repair is involved in maintaining the stability of the genome and accurate sending of genetic information. DNA repair pathways remove many DNA damages induced by endo- and exogenous factors. There are several DNA repair pathways in human cells, including base or nucleotide excision system, homologous recombination system and non-homologous end joining. Mutation in DNA repair genes may results in rare genetic disorders, including Xeroderma pigmentosum, Cockayne syndrom, trichothiodystrophy, Nijmegen syndrome, ataxia teleangiectasia, Werner syndrome, Bloom syndrome, Rothmund-Thomson syndrome. These diseases may be associated with various visual disturbances. In this work we review we focus on human genetic diseases linked with mutations in DNA repair genes associated with visual impairment.
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PMID:[Ocular manifestations in hereditary diseases with defects in DNA repair]. 2534 96