Ataxia Telangiectasia (Louis Bar Syndrome)

An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).

Also Known As:

Networked: 2496 relevant articles (23 outcomes, 122 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neoplasms (Cancer)
2.	Atrophy
3.	Ataxia (Dyssynergia)
4.	Hypercholesterolemia
5.	Burkitt Lymphoma (Burkitt's Lymphoma)

Experts

1.	Shiloh, Yosef: 22 articles (05/2014 - 06/2002)
2.	Lavin, Martin F: 21 articles (09/2015 - 08/2002)
3.	Paull, Tanya T: 19 articles (10/2015 - 11/2003)
4.	Gatti, Richard A: 17 articles (09/2013 - 02/2003)
5.	Lees-Miller, Susan P: 16 articles (01/2015 - 12/2002)
6.	Sleckman, Barry P: 16 articles (02/2013 - 07/2006)
7.	Khanna, Kum Kum: 15 articles (09/2015 - 02/2002)
8.	Kastan, Michael B: 13 articles (10/2015 - 12/2002)
9.	Chessa, Luciana: 13 articles (06/2015 - 08/2002)
10.	Bassing, Craig H: 13 articles (09/2014 - 07/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Ataxia Telangiectasia:

1.	Phosphotransferases (Kinase)IBA 05/01/2015 - "This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. " 03/01/2014 - "Pharmacology studies indicate that Ataxia-telangiectasia mutated and its sister kinase ataxia telangiectasia mutated and Rad3-related up-regulate these neuronal SQ substrates. " 02/01/2014 - "This study examined ataxia telangiectasia mutated (ATM), an apical kinase in the host DNA damage response, as a potential new target for the treatment of HK. " 01/01/2014 - "Recent studies suggest that the ataxia telangiectasia mutant (ATM) kinase is not only a key protein mediating cellular responses to DNA damage, but also regulates cellular senescence induced by telomere end exposure (in RS) or persistent DNA damage (in SIPS). " 09/01/2013 - "In this study, we show that phosphorylation at Thr378 and Ser379 sites is dependent on the ataxia-telangiectasia mutated (ATM) and Rad3-related (ATR), a kinase activated during IBV replication. "
2.	DNA (Deoxyribonucleic Acid)IBA 06/01/2013 - "DNA molecules with the TR sequences constrained in the T-shaped HP conformation at one or both ends were subject to a loss of gene expression, which was partially relieved in ataxia telangiectasia mutated (ATM(-/-)) cells. " 03/26/2015 - "In this study, we show that high levels of TACC3 lead to the accumulation of DNA double-strand breaks (DSBs) and disrupt the normal cellular response to DNA damage, at least in part, by negatively regulating the expression of ataxia telangiectasia mutated (ATM) and the subsequent DNA damage response (DDR) signaling cascade. " 11/01/2011 - "Ataxia telangiectasia mutated (ATM) has multiple functions in homologous recombination (HR) and nonhomologous end joining (NHEJ), which lead to conflicting data regarding its DNA double-strand break-repair (DSBR) functions in previous studies. " 02/01/2008 - "Significantly, recent studies have revealed that activation of ataxia telangiectasia mutated and ataxia telangiectasia Rad3 related could be a central effect of RV that underlies cell-cycle regulation and the newly described activation of fidelity control mechanisms in DNA double-strand break repair involving Nbs1 and p53. " 06/01/2004 - "In this study, 20 families with at least one affected child clinically suspected to have ataxia-telangiectasia were examined and their DNA was extracted and amplified with standard methods. "
3.	Proteins (Proteins, Gene)IBA 09/01/2013 - "In the present study, we investigated the changes of HR DNA repair proteins (ataxia-telangiectasia-mutated; ATM, ATM and Rad3-related; ATR), NHEJ repair proteins (Ku70/80), cell cycle regulators (Chk1, Chk2), and apoptosis marker (p53/p-p53) were determined in H. " 09/01/1999 - "Here, we study the effect of apoptosis on the integrity of two proteins that have critical roles in DNA damage signalling, cell cycle checkpoint controls, and genome maintenance-the product of the gene defective in ataxia telangiectasia, ATM, and the related protein ATR. " 02/01/2015 - "Overall, analysis of all recruited patients showed no marked differences in the phosphorylation of proteins (H2AX, protein 53, and ataxia telangiectasia mutated) after SPECT. " 03/01/2014 - "Phosphorylation of representative DDR-associated proteins, such as ataxia telangiectasia mutated (ATM) and H2AX, was induced as early as 30 min (0.5 h) postinfection and persisted during in vitro KSHV latency. " 12/01/2013 - "Tripartite motif-containing 29 (TRIM29), also known as ataxia-telangiectasia group D, is structurally a member of the tripartite motif family of proteins, which characterized by the conserved RING finger, B-box, and coiled-coil domains. "
4.	Protein Kinases (Protein Kinase)IBA 02/01/2015 - "In the present study, we identified Fe65 Ser(228) as a novel target of the ATM (ataxia telangiectasia mutated) and ATR (ataxia-telangiectasia- and Rad3-related protein) protein kinases, in a reaction that occurred independently of APP. " 04/01/2006 - "Insight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase, ataxia telangiectasia mutated, has been provided by recent studies. " 11/05/1999 - "Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. " 04/01/2015 - "In response to any source of DNA damage, cells must initiate an effective DNA damage response (DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), are major regulators of DNA damage recognition and repair. " 03/13/2015 - "A major response to DNA damage is provided by the protein kinase ATM (ataxia telangiectasia mutated) that is capable of commanding a plethora of signaling networks for DNA repair, cell cycle arrest, and even apoptosis. "
5.	ataxia telangiectasia mutated proteinIBA 12/01/2003 - "Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of nuclear lysates for ATM protein expression." 03/01/2015 - "The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. " 06/01/2000 - "Previous studies on a limited number of ataxia-telangiectasia (A-T) patients with detectable levels of intracellular ATM protein have suggested a genotype/phenotype correlation. " 06/01/2000 - "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity." 03/10/2015 - "Moreover, we quantified cardiomyocyte nuclear foci of phosphorylated ataxia telangiectasia mutated protein, an upstream regulator of the DDR pathway, and we found a significant decrease in the number of nuclear phosphorylated ataxia telangiectasia mutated foci in the post-LVAD hearts. "
6.	Betamethasone (Celestone)FDA Link 04/01/2011 - "This study provides Class IIIA evidence that betamethasone at very low dosage is effective in improving neurological signs of patients affected with ataxia-telangiectasia." 04/01/2011 - "Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia." 05/01/2013 - "Betamethasone therapy in ataxia telangiectasia: unraveling the rationale of this serendipitous observation on the basis of the pathogenesis." 10/01/2006 - "Betamethasone and improvement of neurological symptoms in ataxia-telangiectasia." 10/01/2006 - "To preliminarily determine the effectiveness of corticosteroid therapy on the central nervous system symptoms of a child with ataxia-telangiectasia in whom neurological signs improved when, occasionally, he was given betamethasone to treat asthmatic bronchitis attacks. "
7.	DNA-Activated Protein KinaseIBA 09/01/2013 - "Under these conditions, ataxia-telangiectasia mutated activation and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci suggested an increased number of DSBs processed by nonhomologous end-joining (NHEJ). " 11/01/2003 - "These results did not correlate with radiation-induced apoptosis but did correlate with functional impairment of DNA repair and suppressed expression of several repair-related genes, such as Ku70, DNA-dependent protein kinase, ataxia telangiectasia mutated, and X-ray-sensitive complementation group 4. Normal human fibroblast MRC-9 cells showed no impairment in the repair capability due to Ad-p53 despite the suppression of some repair genes. " 12/01/2001 - "Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase." 09/19/1996 - "The role of Ataxia telangiectasia and the DNA-dependent protein kinase in the p53-mediated cellular response to ionising radiation." 06/15/2008 - "Prognostic significance of ataxia-telangiectasia mutated, DNA-dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86-kD subunit expression in patients with nonsmall cell lung cancer."
8.	Histones (Histone)IBA 04/24/2007 - "We find that gamma-irradiation activates the ataxia telangiectasia mutated-associated DNA damage response pathway in the HPECs but that the clearance of phosphorylated histone H2AX (gammaH2AX) foci is delayed. " 09/03/2013 - "We find that persistent DNA damage in aP2-Ercc1F/- fat depots and in adipocytes ex vivo triggers the induction of proinflammatory factors by promoting transcriptionally active histone marks and the dissociation of nuclear receptor corepressor complexes from promoters; the response is cell autonomous and requires ataxia telangiectasia mutated (ATM). " 10/01/2012 - "The cytotoxicity of these combinations correlates with the activation of the ataxia telangiectasia mutated-CHK2 pathway, phosphorylation of KRAB-associated protein-1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. " 08/01/2012 - "Conversely, mutants in the key DNA damage signalling factor ATM (ATAXIA TELANGIECTASIA MUTATED) display increased histone acetylation upon irradiation, linking the DNA damage response with dynamic changes in histone modification in plants." 06/01/2012 - "Moreover, activation of DNA damage checkpoints (ataxia telangiectasia mutated (ATM) and H2A histone family, member X (H2AFX (H2AFX))) and proliferation index (MIB-1) were quantified in 28 non-oxyphilic and 24 oxyphilic FTCs. "
9.	Caffeine (No Doz)FDA LinkGeneric 03/01/1995 - "Studies involving cells treated with caffeine, cells from humans with the genetic disease ataxia telangiectasia, and cells that are deficient in p53 show no correlation between G1 delay and increased cell killing or chromosome damage in response to ionizing radiation. " 01/01/2011 - "In addition, we found that ATBF1-mediated neuronal death is dependent on ataxia-telangiectasia mutated (ATM) because the blockage of ATM activity by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1 function in neuronal death. " 02/15/2006 - "Moreover, p53 was still stabilized in ataxia telangiectasia cells or in cells treated with caffeine, suggesting that ATM was not a critical determinant. " 09/01/2001 - "Moreover, in control cells caffeine shortened G(2) and increased chromosomal damage 7-fold, while in ataxia telangiectasia cells caffeine only trebled aberration yield without shortening G(2). " 04/07/2000 - "Prior treatment of cells with 2 mM caffeine inhibits such a change and markedly reduces radiation-induced ataxia-telangiectasia-mutated (ATM)-dependent Chk2/Cds1 activation and phosphorylation. "
10.	Reactive Oxygen Species (Oxygen Radicals)IBA 10/01/2013 - "To explore the putative roles of oxidative DNA damage and the ataxia telangiectasia-mutated (ATM) pathways on the OTA-induced G2 arrest, the current study systematically evaluated the roles of reactive oxygen species (ROS) production, DNA damage, and ATM-dependent pathway activation on the OTA-induced G2 phase arrest in GES-1 cells. " 08/10/2010 - "The p53 activation depends on the ataxia-telangiectasia mutated (ATM) gene product and increased levels of reactive oxygen species. " 09/01/2006 - "We previously showed pregnant knockout mice lacking the A-T gene product ataxia-telangiectasia mutated (Atm) are highly susceptible to the embryopathic effects of IR, which damages DNA, possibly via generation of reactive oxygen species (ROS). " 01/01/1994 - "Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions." 08/01/2015 - "Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants."

Therapies and Procedures

1.	Radiotherapy 08/01/2000 - "The cases of two patients who suffered severe late effects of radiotherapy are reported; each tested positive for elevated in vitro radiohypersensitivity (RHS) but negative for the ataxia-telangiectasia mutation. " 08/01/1995 - "We examined the cytotoxic effects of radiation delivered in daily fractions at clinically relevant doses in plateau phase cultures of skin fibroblast cell strains derived from ataxia telangiectasia (AT) heterozygotes, patients with unusually sensitive responses to radiotherapy, apparently normal patients, and cell bank controls. " 08/01/1995 - "Response of dermal fibroblast cultures from patients with unusually severe responses to radiotherapy and from ataxia telangiectasia heterozygotes to fractionated radiation." 10/01/1991 - "Ataxia-telangiectasia (A-T) is a rare human autosomal recessive disorder characterized by, among other symptoms, catastrophic reaction to conventional radiotherapy. " 03/01/1991 - "These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. "
2.	Drug Therapy (Chemotherapy) 02/01/2012 - "Patients with ataxia-telangiectasia (A-T) have an increased risk of developing malignancies and are prone to severe early or late toxicity owing to chemotherapy. " 09/01/1988 - "Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. " 07/29/2005 - "Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. " 02/01/2014 - "Ionizing radiation and chemotherapy activate AMPK in cancer cells to mediate signal transduction downstream of ataxia telangiectasia mutated (ATM) to activate p53- p21(cip1)/p27(kip1) and inhibit mTOR. " 03/15/2008 - "Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy."
3.	Aftercare (After-Treatment) 01/01/2010 - "After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of ataxia telangiectasia mutated (ATM) and p53. " 07/01/2004 - "Osteosarcoma as a second tumor after treatment for primary non-Hodgkin's lymphoma in a child with ataxia-telangiectasia: presentation of a case and review of possible pathogenetic mechanisms." 04/08/2005 - "Previous studies have indicated that both the ataxia telangiectasia mutated (ATM)/checkpoint kinase (Chk) 2 and ATM- and Rad 3-related (ATR)/Chk1 checkpoint pathways are activated after treatment with these agents. " 05/28/2015 - "The primary signalling cascade responding to replication stress in malignant cells (ataxia telangiectasia-mutated (ATM) and Rad3-related-checkpoint kinase 1 (ATR-CHK1)) is not activated in hTERT-NHU cells after treatment with a replication inhibitor and these cells do not depend upon CHK1 for protection from apoptosis during replication stress. " 01/01/1982 - "Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. "
4.	Transplantation (Transplant Recipients) 01/01/1971 - "[Clinical-immunological study and transplantation of the thymus in the Louis-Bar syndrome]." 01/01/1984 - "Other patients with immune deficiency syndromes, i.e., ataxia telangiectasia or the renal transplant recipient, are also at increased risk for developing EBV-induced lymphoproliferative diseases. " 01/01/1973 - "[Clinico-immunologic indices in patients with the Louis-Bar syndrome following transplantation of the thymus and sternum]." 07/29/2005 - "Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. " 02/17/2009 - "Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient."
5.	Brachytherapy 01/01/2005 - "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. " 01/01/2011 - "This program consists of (a) a culturally tailored patient navigation program that facilitated access to innovative clinical trials in conjunction with a comprehensive educational program encouraging screening and early detection, (b), surveys to evaluate barriers to access, (c) clinical trials focusing on reducing treatment length to facilitate enhanced participation using brachytherapy and intensity modulated radiotherapy (IMRT) for breast and prostate cancer, as AIs live a median of 140 miles from the cancer center, and (d) a molecular study (ataxia telangiectasia mutated) to address whether there is a specific profile that increases toxicity risks. "