Description:
ATAXIA-TELANGIECTASIA; AT
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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 |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Family Member
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3
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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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| PDL at Freeze |
8.24 |
| Passage Frozen |
6 |
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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 |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 1 |
S381fsX; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
1141ins4 |
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| Gene |
ATM |
| Chromosomal Location |
11q22.3 |
| Allelic Variant 2 |
LYS2756TER; ATAXIA-TELANGIECTASIA |
| Identified Mutation |
8266A>T |
| 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;
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Kaufmann WK, Wilson SJ, G1 arrest and cell-cycle-dependent clastogenesis in UV-irradiated human fibroblasts. Mutat Res314:67-76 1994 |
| PubMed ID: 7504193 |
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| 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 |
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| 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 |
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| 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 |
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| Meredith MJ, Dodson ML, Imparied glutathione biosynthesis in cultured human ataxia- telangiectasia cells. Cancer Res47:4576-81 1987 |
| PubMed ID: 3621155 |
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| 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 |
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| McKinnon PJ, Burgoyne LA, Altered cellular morphology and microfilament array in ataxia- telangiectasia fibroblasts. Eur J Cell Biol39:161-6 1985 |
| PubMed ID: 3910438 |
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| 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 |
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| 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 |
| dbSNP |
dbSNP ID: 18963 |
| NCBI GTR |
208900 ATAXIA-TELANGIECTASIA; AT |
| OMIM |
208900 ATAXIA-TELANGIECTASIA; AT |
| 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 |
| Passage Frozen |
6 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM |
| Serum |
15% fetal bovine serum Not inactivated |
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