Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Chromosome Abnormalities
Class Repair Defective and Chromosomal Instability Syndromes
Class Syndromes with Increased Chromosome Breakage
Cell Type Fibroblast
Transformant Untransformed
Race Caucasian
Family Member 3
Relation to Proband proband
Confirmation Clinical summary/Case history
Species Homo sapiens
Common Name Human
Remarks AT4Be; clinically affected; neurological abnormalities; 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 GM03189 for donor LCL;
Passage Frozen 11
 
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis
 
Gene ATM
Chromosomal Location 11q22.3
Allelic Variant 1 S381fsX; ATAXIA-TELANGIECTASIA
Identified Mutation 1141ins4
 
Gene ATM
Chromosomal Location 11q22.3
Allelic Variant 2 LYS2756TER; ATAXIA-TELANGIECTASIA
Identified Mutation 8266A>T
Remark AT4Be; clinically affected; neurological abnormalities; 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 GM03189 for donor LCL;
Pintado-Berninches L, Fernandez-Varas B, Benitez-Buelga C, Manguan-Garcia C, Serrano-Benitez A, Iarriccio L, Carrillo J, Guenechea G, Egusquiaguirre SP, Pedraz JL, Hernández RM, Igartua M, Arias-Salgado EG, Cortés-Ledesma F, Sastre L, Perona R, GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells Cell death and differentiation: 2018
PubMed ID: 30670828
 
Wilson PF, Nham PB, Urbin SS, Hinz JM, Jones IM, Thompson LH, Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation Mutation research683:91-7 2009
PubMed ID: 19896956
 
Kim HS, Li H, Cevher M, Parmelee A, Fonseca D, Kleiman FE, Lee SB, DNA damage-induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex Cancer research66:4561-5 2006
PubMed ID: 16651405
 
Tanaka H, Mendonca MS, Bradshaw PS, Hoelz DJ, Malkas LH, Meyn MS, Gilley D, DNA damage-induced phosphorylation of the human telomere-associated protein TRF2 Proceedings of the National Academy of Sciences of the United States of America102:15539-44 2005
PubMed ID: 16223874
 
Powers JT, Hong S, Mayhew CN, Rogers PM, Knudsen ES, Johnson DG, E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis. Mol Cancer Res2(4):203-14 2004
PubMed ID: 15140942
 
Peretz S, Jensen R, Baserga R, Glazer PM, ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc Natl Acad Sci U S A98(4):1676-81 2001
PubMed ID: 11172010
 
Gately DP, Hittle JC, Chan GK, Yen TJ, Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity. Mol Biol Cell9:2361-74 1998
PubMed ID: 9725899
 
Rhodes N, D'Souza T, Foster CD, Ziv Y, Kirsch DG, Shiloh Y, Kastan MB, Reinhart PH, Gilmer TM, Defective potassium currents in ataxia telangiectasia fibroblasts. Genes Dev12:3686-92 1998
PubMed ID: 9851975
 
Vaziri H, West MD, Allsopp RC, Davison TS, Wu YS, Arrowsmith CH, Poirier GG, Benchimol S, ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J16:6018-33 1997
PubMed ID: 9312059
 
Kaufmann WK, Wilson SJ, G1 arrest and cell-cycle-dependent clastogenesis in UV-irradiated human fibroblasts. Mutat Res314:67-76 1994
PubMed ID: 7504193
 
Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993
PubMed ID: 8242748
 
Kaufmann WK, Boyer JC, Estabrooks LL, Wilson SJ, Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes. Mol Cell Biol11:3711-8 1991
PubMed ID: 1646393
 
Bender MA, Viola MV, Fiore J, Thompson MH, Leonard RC, Normal G2 chromosomal radiosensitivity and cell survival in the cancer family syndrome [see comments] Cancer Res48:2579-84 1988
PubMed ID: 3356018
 
Meredith MJ, Dodson ML, Imparied glutathione biosynthesis in cultured human ataxia- telangiectasia cells. Cancer Res47:4576-81 1987
PubMed ID: 3621155
 
Nagasawa H, Latt SA, Lalande ME, Little JB, Effects of X-irradiation on cell-cycle progression, induction of chromosomal aberrations and cell killing in ataxia telangiectasia (AT) fibroblasts. Mutat Res148:71-82 1985
PubMed ID: 3969079
 
McKinnon PJ, Burgoyne LA, Altered cellular morphology and microfilament array in ataxia- telangiectasia fibroblasts. Eur J Cell Biol39:161-6 1985
PubMed ID: 3910438
 
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
 
Kinsella TJ, Mitchell JB, McPherson S, Russo A, Tietze F, In vitro X-ray sensitivity in ataxia telangiectasis homozygote and heterozygote skin fibroblasts under oxic and hypoxic conditions. Cancer Res42:3950-6 1982
PubMed ID: 7104995
No data is available
Passage Frozen 11
Split Ratio 1:3
Temperature 37 C
Percent CO2 5%
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 15% fetal bovine serum Not inactivated
Substrate None specified
Subcultivation Method trypsin-EDTA