Disease relevance of Ataxia Telangiectasia

• Mutations in atm and p53 cause the human cancer-associated diseases ataxia-telangiectasia and Li-Fraumeni syndrome, respectively [1].
• Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers [2].
• Analogous to E1A expression, DNA damage down-regulates MCL-1, and adenovirus infection resulted in the accumulation of phosphorylated H2AX and ataxia-telangiectasia mutant protein (ATM), hallmarks of DNA double-strand breaks [3].
• While NBS shares overlapping characteristics with ataxia telangiectasia, it also has features overlapping with ATR-Seckel (ATR: ataxia-telangiectasia and Rad3-related protein) syndrome, a subclass of Seckel syndrome mutated in ATR [4].
• To facilitate the evaluation of ATM heterozygotes for susceptibility to other diseases, such as breast cancer, we have attempted to define the most common mutations and their frequencies in ataxia-telangiectasia (A-T) homozygotes from 10 ethnic populations [5].

Psychiatry related information on Ataxia Telangiectasia

• It includes at least four distinct genetic entities: ataxia-telangiectasia, ataxia-telangiectasia-like disorder, and ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) [6].

High impact information on Ataxia Telangiectasia

• This 'radioresistant DNA synthesis' (RDS) is a phenotypic hallmark of ataxia-telangiectasia, a cancer-prone disorder caused by mutations in ATM [7].
• The gene encoding ataxia-telangiectasia and Rad3-related protein (ATR) maps to this region [8].
• Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer [9].
• In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells [10].
• A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia [10].

Chemical compound and disease context of Ataxia Telangiectasia

• Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase [11].
• In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5 [12].
• We tested this hypothesis by determining whether the well-described nitroxide antioxidant, tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), acts as a chemopreventative agent in Atm mutant mice, a model of the human cancer prone syndrome ataxia-telangiectasia [13].
• Re: Impaired glutathione biosynthesis in cultured ataxia-telangiectasia cells [14].
• The similarity of these checkpoint defects to those seen in ataxia-telangiectasia (A-T) suggested that caffeine might inhibit one or more components in an A-T mutated (ATM)-dependent checkpoint pathway in DNA-damaged cells [15].

Biological context of Ataxia Telangiectasia

• ATM deficiency causes the genetic disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency, radiation sensitivity, chromosomal instability and cancer predisposition [16].
• We find that Xmus101 is essential for AT70-mediated checkpoint signaling and that it functions to promote phosphorylation of Claspin bound Chk1 by the ataxia-telangiectasia and Rad-3-related (ATR) protein kinase [17].
• ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome [18].
• This technique has been used for rapid correlation of the genetic and physical map of chromosome 11q13-qter in the region of genes responsible for ataxia-telangiectasia and tuberous sclerosis [19].
• The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding to the deduced amino acid sequence [20].

Anatomical context of Ataxia Telangiectasia

• ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer [21].
• Degeneration of neurons, synapses, and neuropil and glial activation in a murine Atm knockout model of ataxia-telangiectasia [22].
• The multiplicity of hMre11 and hRad50 foci is much higher in the DSB repair-deficient cell line 180BR than in repair-proficient cells. hMre11-hRad50 focus formation is markedly reduced in cells derived from ataxia-telangiectasia patients, whereas hRad51 focus formation is markedly increased [23].
• Hypersensitivity to cell killing and faulty repair of 1-beta-D-arabinofuranosylcytosine-detectable sites in human (ataxia-telangiectasia) fibroblasts treated with 4-nitroquinoline 1-oxide [24].
• We analyzed the role of 4 genes, TCL-1, MTCP-1, TML-1 and ATM, in the early pathogenesis of T cell leukemia, with particular interest in the characteristics of long-standing non-leukemic clonal proliferations in ataxia-telangiectasia (A-T) patients [25].

Gene context of Ataxia Telangiectasia

• Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products [26].
• MEC1 is similar in sequence to human ATM, the gene mutated in patients with ataxia-telangiectasia (A-T) [27].
• We report here direct interaction between BLM, mutated in Bloom's Syndrome (BS), and ATM, mutated is ataxia-telangiectasia, and we have mapped the sites of interaction [28].
• Chromosomal locations of the Atm (ataxia-telangiectasia (AT)-mutated) and Acat1 (mitochondrial acetoacetyl-CoA thiolase) genes in mouse, rat, and Syrian hamster were determined by direct R-banding FISH [29].
• Recently, a cell cycle checkpoint pathway involving p53 and GADD45 has been identified as defective in ataxia-telangiectasia [30].

Analytical, diagnostic and therapeutic context of Ataxia Telangiectasia

• BACKGROUND: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer [31].
• We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein [32].
• To investigate the neuropathology of ataxia-telangiectasia, we used in situ hybridization to map Atm (the gene mutated in ataxia-telangiectasia) expression during mouse development [33].
• PURPOSE: To examine whether the presence of sequence variants in the ATM (mutated in ataxia-telangiectasia) gene is predictive for the development of radiation-induced adverse responses resulting from (125)I prostate brachytherapy for early-stage prostate cancer [34].
• Lymphocyte surface proteins of patients with ataxia-telangiectasia were separated by polyacrylamide gel electrophoresis and compared by autoradiography [35].

References