Description:
ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM
TRANSLOCATED CHROMOSOME
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Class |
Syndromes with Increased Chromosome Breakage |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
MET1THR; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
2T>C;no initiation |
| Remarks |
a T>C substitution at nucleotide 2 (2T>C) in exon 4 abolishes the initiation codon (Met1Thr); AT8BI; 46,XX,t(X;14) clone in short term lymphocytes; HLA type A9,A10,Bw17, B13(Bw40); exhibits increased chromosomal radiation sensitivity; increased chromosome breakage induced by bleomycin. |
| Sinha A, Saleh A, Endersby R, Yuan SH, Chokshi CR, Brown KR, Kuzio B, Kauppinen T, Singh SK, Baker SJ, McKinnon PJ, Katyal S, RAD51-Mediated DNA Homologous Recombination Is Independent of Cancers12: 2020 |
| PubMed ID: 33138032 |
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| JunGang Z, Jun T, WanFu M, KaiMing R, FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells FEBS letters586:4257-63 2012 |
| PubMed ID: 23108047 |
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| Boehme KA, Kulikov R, Blattner C, p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK Proceedings of the National Academy of Sciences of the United States of America105:7785-90 2008 |
| PubMed ID: 18505846 |
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| Gatz SA, Keimling M, Baumann C, Dörk T, Debatin KM, Fulda S, Wiesmüller L, Resveratrol modulates DNA double-strand break repair pathways in an ATM/ATR-p53- and -Nbs1-dependent manner Carcinogenesis29:519-27 2008 |
| PubMed ID: 18174244 |
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| Helt CE, Cliby WA, Keng PC, Bambara RA, O'Reilly MA, Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage J Biol Chem280(2):1186-92 2005 |
| PubMed ID: 15533933 |
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| Jen KY, Cheung VG, Identification of novel p53 target genes in ionizing radiation response. Cancer Res65(17):7666-73 2005 |
| PubMed ID: 16140933 |
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| Marcelain K, De La Torre C, González P, Pincheira J, Roles of nibrin and AtM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage Biological research38:179-85 2005 |
| PubMed ID: 16238096 |
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| Tu LC, Matsui SI, Beerman TA, Hedamycin, a DNA alkylator, induces (gamma)H2AX and chromosome aberrations: involvement of phosphatidylinositol 3-kinase-related kinases and DNA replication fork movement Molecular cancer therapeutics4:1175-85 2005 |
| PubMed ID: 16093433 |
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| Ismail IH, Nyström S, Nygren J, Hammarsten O, Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks The Journal of biological chemistry280:4649-55 2004 |
| PubMed ID: 15546858 |
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| Lau A, Swinbank KM, Ahmed PS, Taylor DL, Jackson SP, Smith GC, O'Connor MJ, Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase Nature cell biology7:493-500 2004 |
| PubMed ID: 15834407 |
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| Leonard JC, Mullinger AM, Schmidt J, Cordell HJ, Johnson RT, Genome instability in ataxia telangiectasia (A-T) families: camptothecin-induced damage to replicating DNA discriminates between obligate A-T heterozygotes, A-T homozygotes and controls. Biosci Rep24(6):617-29 2004 |
| PubMed ID: 16158199 |
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| Yuan JH, Feng Y, Fisher RH, Maloid S, Longo DL, Ferris DK, Polo-like kinase 1 inactivation following mitotic DNA damaging treatments is independent of ataxia telangiectasia mutated kinase Molecular cancer research : MCR2:417-26 2004 |
| PubMed ID: 15280449 |
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| Zhu Y, Alvarez C, Doll R, Kurata H, Schebye XM, Parry D, Lees E, Intra-S-phase checkpoint activation by direct CDK2 inhibition. Mol Cell Biol24(14):6268-77 2004 |
| PubMed ID: 15226429 |
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| Ismail IH, Mårtensson S, Moshinsky D, Rice A, Tang C, Howlett A, McMahon G, Hammarsten O, SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break repair resulting in ionizing radiation sensitization Oncogene23:873-82 2003 |
| PubMed ID: 14661061 |
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| Hammond EM, Denko NC, Dorie MJ, Abraham RT, Giaccia AJ, Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol22(6):1834-43 2002 |
| PubMed ID: 11865061 |
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| Saito S, Goodarzi AA, Higashimoto Y, Noda Y, Lees-Miller SP, Appella E, Anderson CW, ATM mediates phosphorylation at multiple p53 sites, including Ser(46), in response to ionizing radiation. J Biol Chem277(15):12491-4 2002 |
| PubMed ID: 11875057 |
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| Gottifredi V, Shieh S, Taya Y, Prives C, From the Cover: p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc Natl Acad Sci U S A98(3):1036-41 2001 |
| PubMed ID: 11158590 |
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| Lin WC, Lin FT, Nevins JR, Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev15(14):1833-44 2001 |
| PubMed ID: 11459832 |
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| Zhao H, Spitz MR, Tomlinson GE, Zhang H, Minna JD, Wu X, Gamma-radiation-induced G2 delay, apoptosis, and p53 response as potential susceptibility markers for lung cancer. Cancer Res61(21):7819-24 2001 |
| PubMed ID: 11691798 |
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| Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, Roberts TM, Swat W, Segal RA, Gu Y, Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A97:3336-41 2000 |
| PubMed ID: 10716718 |
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| Narayan A, Tuck-Muller C, Weissbecker K, Smeets D, Ehrlich M, Hypersensitivity to radiation-induced non-apoptotic and apoptotic death in cell lines from patients with the ICF chromosome instability syndrome Mutation research456:1-15 2000 |
| PubMed ID: 11087891 |
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| Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T, p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science283(5406):1321-5 1999 |
| PubMed ID: 10037601 |
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| Myung K, Braastad C, He DM, Hendrickson EA, KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion. Proc Natl Acad Sci U S A95:7664-9 1998 |
| PubMed ID: 9636207 |
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| Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB, DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev11:3471-81 1997 |
| PubMed ID: 9407038 |
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| Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A, Predominance of null mutations in ataxia-telangiectasia. Hum Mol Genet5(4):433-9 1996 |
| PubMed ID: 8845835 |
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| Antoccia A, Chessa L, Ricordy R, Tanzarella C, Modulation of radiation-induced chromosomal damage by inhibitors of DNA repair and flow cytometric analysis in ataxia telangiectasia cells with 'intermediate radiosensitivity'. Mutagenesis10:523-9 1995 |
| PubMed ID: 8596472 |
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| Pandita TK, Hittelman WN, Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells. Mutat Res310:1-13 1994 |
| PubMed ID: 7523872 |
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| Caporossi D, Porfirio B, Nicoletti B, Palitti F, Degrassi F, De Salvia R, Tanzarella C, Hypersensitivity of lymphoblastoid lines derived from ataxia telangiectasia patients to the induction of chromosomal aberrations by etoposide (VP-16) Mutation research290:265-72 1993 |
| PubMed ID: 7694118 |
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| Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ Jr, A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell71:587-97 1992 |
| PubMed ID: 1423616 |
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| Cohen NA, Egorin MJ, Snyder SW, Ashar B, Wietharn BE, Pan SS, Ross DD, Hilton J, Interaction of N,N',N''-triethylenethiophosphoramide and N,N',N''- triethylenephosphoramide with cellular DNA. Cancer Res51:4360-6 1991 |
| PubMed ID: 1714342 |
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| Hsu TC, Furlong C, The role of ethanol in oncogenesis of the upper aerodigestive tract; inhibition of DNA repair. Anticancer Res11:1995-8 1991 |
| PubMed ID: 1776831 |
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| Metcalfe JA, Heppell-Parton A, McConville CM, Taylor AM, Characterization of a B-lymphocyte t(2;14) (p11;q32) translocation from an ataxia telangiectasia patient conferring a proliferative advantage on cells in vitro. Cytogenet Cell Genet56:91-8 1991 |
| PubMed ID: 1901542 |
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| Karam LR, Calsou P, Franklin WA, Painter RB, Olsson M, Lindahl T, Modification of deoxyribose-phosphate residues by extracts of ataxia telangiectasia cells. Mutat Res236:19-26 1990 |
| PubMed ID: 2366795 |
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| Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA, Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress. Cancer Res49:5239-43 1989 |
| PubMed ID: 2766291 |
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| Smith PJ, Makinson TA, Cellular consequences of overproduction of DNA topoisomerase II in an ataxia-telangiectasia cell line. Cancer Res49:1118-24 1989 |
| PubMed ID: 2537142 |
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| Willis AE, Lindahl T, DNA ligase I deficiency in Bloom's syndrome. Nature325:355-7 1987 |
| PubMed ID: 3808031 |
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| McKinnon PJ, Burgoyne LA, Evidence for the existence of an actin-derived protein in ataxia- telangiectasia lymphoblastoid cell lines. Exp Cell Res158:413-22 1985 |
| PubMed ID: 2988987 |
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| Smith PJ, Anderson CO, Watson JV, Effects of X-irradiation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells. Exp Cell Res160:331-42 1985 |
| PubMed ID: 2412868 |
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| Cohen MM, Simpson SJ, Increased clastogenicity and decreased inhibition of DNA synthesis by neocarzinostatin and tallysomycin in ataxia telangiectasia lymphoid cells. Mutat Res112:119-28 1983 |
| PubMed ID: 6188042 |
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| Zwelling LA, Kerrigan D, Mattern MR, Ataxia-telangiectasia cells are not uniformly deficient in poly(ADP- ribose) synthesis following X-irradiation. Mutat Res120:69-78 1983 |
| PubMed ID: 6835265 |
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| Cohen MM, Fruchtman CE, Simpson SJ, Martin AO, The cytogenetic response of Fanconi's anemia lymphoblastoid cell lines to various clastogens. Cytogenet Cell Genet34:230-40 1982 |
| PubMed ID: 6183057 |
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| Cohen MM, Simpson SJ, Pazos L, Specificity of bleomycin-induced cytotoxic effects on ataxia telangiectasia lymphoid cell lines. Cancer Res41:1817-23 1981 |
| PubMed ID: 6163529 |
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| Edwards MJ, Taylor AM, Flude EJ, Bleomycin induced inhibition of DNA synthesis in ataxia-telangiectasia cell lines. Biochem Biophys Res Commun102:610-6 1981 |
| PubMed ID: 6171286 |
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| Huang, Genetic and biochemical studies with ataxia telangiectasia: A review. Hum Genet59:1-9 1981 |
| PubMed ID: 10819014 |
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| Littlefield LG, Colyer SP, Joiner EE, DuFrain RJ, Frome E, Cohen MM, Chromosomal radiation sensitivity in ataxia telangiectasia long-term lymphoblastoid cell lines. Cytogenet Cell Genet31:203-13 1981 |
| PubMed ID: 6978798 |
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| Cohen, Absence of a clastogenic factor in ataxia telangiectasia lymphoblastoid cells. Cancer Genet Cytogenet2:327-334 1980 |
| PubMed ID: 6978798 |
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| Edwards MJ, Taylor AM, Unusual levels of (ADP-ribose)n and DNA synthesis in ataxia telangiectasia cells following gamma-ray irradiation. Nature287:745-7 1980 |
| PubMed ID: 7432491 |
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| Cohen MM, Sagi M, Ben-Zur Z, Schaap T, Voss R, Kohn G, Ben-Bassat H, Ataxia telangiectasia: chromosomal stability in continuous lymphoblastoid cell lines. Cytogenet Cell Genet23:44-52 1979 |
| PubMed ID: 761484 |
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| Oxford JM, Harnden DG, Parrington JM, Delhanty JD, Specific chromosome aberrations in ataxia telangiectasia. J Med Genet12:251-62 1975 |
| PubMed ID: 1177276 |
| dbSNP |
dbSNP ID: 10414 |
| Gene Cards |
ATM |
| Gene Ontology |
GO:0003677 DNA binding |
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GO:0003700 transcription factor activity |
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GO:0004674 protein serine/threonine kinase activity |
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GO:0005622 intracellular |
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GO:0005634 nucleus |
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GO:0006281 DNA repair |
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GO:0006355 regulation of transcription, DNA-dependent |
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GO:0007131 meiotic recombination |
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GO:0007165 signal transduction |
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GO:0016740 transferase activity |
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GO:0016773 phosphotransferase activity, alcohol group as acceptor |
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GO:0045786 negative regulation of cell cycle |
| NCBI Gene |
Gene ID:472 |
| NCBI GTR |
208900 ATAXIA-TELANGIECTASIA; AT |
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607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| OMIM |
208900 ATAXIA-TELANGIECTASIA; AT |
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607585 ATAXIA-TELANGIECTASIA MUTATED GENE; ATM |
| Omim Description |
AT, COMPLEMENTATION GROUP A, INCLUDED; ATA, INCLUDED |
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AT, COMPLEMENTATION GROUP C, INCLUDED; ATC, INCLUDED |
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AT, COMPLEMENTATION GROUP D, INCLUDED; ATD, INCLUDED |
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AT, COMPLEMENTATION GROUP E, INCLUDED; ATE, INCLUDED |
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AT1 |
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ATAXIA-TELANGIECTASIA; AT |
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LOUIS-BAR SYNDROMEATAXIA-TELANGIECTASIA MUTATED, INCLUDED; ATM, INCLUDED |
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