GM03189

GM03189 LCL from B-Lymphocyte

Description:

ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM

Affected:

Yes

Sex:

Male

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities

Class

Repair Defective and Chromosomal Instability Syndromes

Class

Syndromes with Increased Chromosome Breakage

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

AT4Be; clinically affected; neurological abnormalities; lymphoid culture shows hypersensitivity to X-irradiation; compound heterozygote; the maternal allele carries an A>T substitution at nucleotide 8266 (8266A>T) in exon 58 resulting in a truncation at codon 2756 [Lys2756Ter (K2756X)] and the paternal allele carries a 4bp insertion at nucleotide 1141 in exon 11 resulting in a frameshift at codon 381 leading to a truncation (S381fsX); similarly affected sibling (not in repository); 3 other unaffected sibilings are in repository (see family 516); father(GM03187-LCL/GM03488-Fibro) and mother(GM03188-LCL/GM03489-Fibro) are unaffected carriers; see GM03487 for donor Fibroblast;

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227.

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 1

LYS2756TER; ATAXIA-TELANGIECTASIA

Identified Mutation

8266A>T

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 2

S381fsX; ATAXIA-TELANGIECTASIA

Identified Mutation

1141ins4

Phenotypic Data

Remarks

Publications

Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics: 2021

PubMed ID: 35394024

Asumen MG, Ifeacho TV, Cockerham L, Pfandl C, Wall NR, Dynamic changes to survivin subcellular localization are initiated by DNA damage OncoTargets and therapy3:129-37 2010

PubMed ID: 20856848

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

Pennarun G, Granotier C, Hoffschir F, Mandine E, Biard D, Gauthier LR, Boussin FD, Role of ATM in the telomere response to the G-quadruplex ligand 360A Nucleic acids research36:1741-54 2008

PubMed ID: 18263609

Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna N, Saggar A, Hamel B, Earnshaw WC, Jeggo PA, Jackson AP, O'Driscoll M, Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling Nature genetics40:232-6 2007

PubMed ID: 18157127

Ho CC, Siu WY, Lau A, Chan WM, Arooz T, Poon RY, Stalled replication induces p53 accumulation through distinct mechanisms from DNA damage checkpoint pathways Cancer research66:2233-41 2006

PubMed ID: 16489026

Innes CL, Heinloth AN, Flores KG, Sieber SO, Deming PB, Bushel PR, Kaufmann WK, Paules RS, ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts. Mol Cancer Res4(3):197-207 2006

PubMed ID: 16547157

Jen KY, Cheung VG, Identification of novel p53 target genes in ionizing radiation response. Cancer Res65(17):7666-73 2005

PubMed ID: 16140933

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

Stiff T, Reis C, Alderton GK, Woodbine L, O'Driscoll M, Jeggo PA, Nbs1 is required for ATR-dependent phosphorylation events. EMBO J24(1):199-208 2005

PubMed ID: 15616588

Alderton GK, Joenje H, Varon R, Borglum AD, Jeggo PA, O'Driscoll M, Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet13(24):3127-38 2004

PubMed ID: 15496423

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

Ng CP, Lee HC, Ho CW, Arooz T, Siu WY, Lau A, Poon RY, Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains. J Biol Chem279(10):8808-19 2004

PubMed ID: 14681223

Siu WY, Lau A, Arooz T, Chow JP, Ho HT, Poon RY, Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms. Mol Cancer Ther3(5):621-32 2004

PubMed ID: 15141020

Angele S, Romestaing P, Moullan N, Vuillaume M, Chapot B, Friesen M, Jongmans W, Cox DG, Pisani P, Gerard JP, Hall J, ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer Res63(24):8717-25 2003

PubMed ID: 14695186

Chow JP, Siu WY, Fung TK, Chan WM, Lau A, Arooz T, Ng CP, Yamashita K, Poon RY, DNA damage during the spindle-assembly checkpoint degrades CDC25A, inhibits cyclin-CDC2 complexes, and reverses cells to interphase. Mol Biol Cell14(10):3989-4002 2003

PubMed ID: 14517313

Pichierri P, Rosselli F, Franchitto A, Werner's syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replication arrest and DNA damage induced during the S phase of the cell cycle Oncogene22:1491-500 2003

PubMed ID: 12629512

Wang W, Takimoto R, Rastinejad F, El-Deiry WS, Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding. Mol Cell Biol23(6):2171-81 2003

PubMed ID: 12612087

Franchitto A, Pichierri P, Bloom's syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. J Cell Biol157(1):19-30 2002

PubMed ID: 11916980

Deming PB, Cistulli CA, Zhao H, Graves PR, Piwnica-Worms H, Paules RS, Downes CS, Kaufmann WK, The human decatenation checkpoint. Proc Natl Acad Sci U S A98(21):12044-9 2001

PubMed ID: 11593014

Dantzer F, Menissier-de Murcia J, Barlow C, Wynshaw-Boris A, de Murcia G, Poly(ADP-ribose) polymerase activity is not affected in ataxia telangiectasia cells and knockout mice. Carcinogenesis20:177-80 1999

PubMed ID: 9934867

Will O, Mahler HC, Arrigo AP, Epe B, Influence of glutathione levels and heat-shock on the steady-state levels of oxidative DNA base modifications in mammalian cells. Carcinogenesis20:333-7 1999

PubMed ID: 10069473

Hacia JG, Sun B, Hunt N, Edgemon K, Mosbrook D, Robbins C, Fodor SP, Tagle DA, Collins FS, Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays. Genome Res8(12):1245-58 1998

PubMed ID: 9872980

Sasaki T, Tian H, Kukita Y, Inazuka M, Tahira T, Imai T, Yamauchi M, Saito T, Hori T, Hashimoto-Tamaoki T, Komatsu K, Nikaido O, Hayashi K, ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. Hum Mutat12(3):186-95 1998

PubMed ID: 9711876

Concannon P, Gatti RA, Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat10(2):100-7 1997

PubMed ID: 9259193

Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J, Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Mol Cell Biol17(9):5016-22 1997

PubMed ID: 9271379

Wei S, Charmley P, Concannon P, Organization, polymorphism, and expression of the human T-cell receptor AV1 subfamily. Immunogenetics45(6):405-12 1997

PubMed ID: 9089098

Chen G, Lee EYHP, The product of the ATM gene is a 370-kDa nuclear phosphoprotein. J Biol Chem271:33693-7 1996

PubMed ID: 8969240

Telatar M, Wang Z, Udar N, Liang T, Bernatowska-Matuszkiewicz E, Lavin M, Shiloh Y, Concannon P, Good RA, Gatti RA, Ataxia-telangiectasia: mutations in ATM cDNA detected by protein- truncation screening. Am J Hum Genet59:40-4 1996

PubMed ID: 8659541

Wright J, Teraoka S, Onengut S, Tolun A, Gatti RA, Ochs HD, Concannon P, A high frequency of distinct ATM gene mutations in ataxia- telangiectasia. Am J Hum Genet59:839-46 1996

PubMed ID: 8808599

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

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

Meredith MJ, Dodson ML, Imparied glutathione biosynthesis in cultured human ataxia- telangiectasia cells. Cancer Res47:4576-81 1987

PubMed ID: 3621155

Berliner N, Duby AD, Morton CC, Leder P, Seidman JG, Detection of a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta chain locus. A potential diagnostic tool. J Clin Invest76:1283-5 1985

PubMed ID: 2995449

Kraemer KH, Soares N, Waters HL, Bustin M, Effect of X-radiation on DNA and histone synthesis in ataxia telangiectasia and normal lymphoblastoid cells. Mutat Res112:359-67 1983

PubMed ID: 6656798

Kohn PH, Kraemer KH, Buchanan JK, Influence of ataxia telangiectasia gene dosage on bleomycin-induced chromosome breakage and inhibition of replication in human lymphoblastoid cell lines. Exp Cell Res137:387-95 1982

PubMed ID: 6173245

Kraemer KH, Waters HL, Buchanan JK, Survival of human lymphoblastoid cells after DNA damage measured by growth in microtiter wells. Mutat Res72:285-94 1980

PubMed ID: 6160397