Description:
NIJMEGEN BREAKAGE SYNDROME
NIJMEGEN BREAKAGE SYNDROME GENE; NBS1
|
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
|
White
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| PDL at Freeze |
5.65 |
| Passage Frozen |
10 |
| |
| REPAIR OF UV- OR X RAY-IRRADIATED DNA OR ALKYLATED DNA |
Nove et al (Mutation Res 163:255-262,1986) reported that cells from this patient were found to resemble those from individuals with Ataxia telangiectasia (AT) in terms of their sensitivity to cell killing and the induction of cytogenetic abnormalities by X-rays. Their response to other DNA-damaging agents, including 254-nm light, mitomycin C, MNNG, and bleomycin was also AT-like. In contrast to classical AT, however, X-irradiated cells exhibited a G1 block after release from density inhibition of growth that was not significantly different from that of normal controls. |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
| |
| Gene |
NBS1 |
| Chromosomal Location |
8q21 |
| Allelic Variant 1 |
602667.0001; NIJMEGEN BREAKAGE SYNDROME |
| Identified Mutation |
5-BP DEL, NT657-661; In Nijmegen breakage syndrome (NBS; 251260) patients of
Slavic origin, Varon et al. [Cell 93: 467-476, (1998)] identified a common
deletion of 5 nucleotides in exon 6 of the NBS1 gene, resulting in a
frameshift and a truncated protein. The deletion introduced a premature
termination signal at codon 218, which was predicted to result in a
severely truncated polypeptide. The truncating 5-bp deletion (657del5)
had been identified in 90% of NBS patients. |
| |
| Gene |
NBS1 |
| Chromosomal Location |
8q21 |
| Allelic Variant 2 |
602667.0001; NIJMEGEN BREAKAGE SYNDROME |
| Identified Mutation |
5-BP DEL, NT657-661; In Nijmegen breakage syndrome (NBS; 251260) patients of
Slavic origin, Varon et al. [Cell 93: 467-476, (1998)] identified a common
deletion of 5 nucleotides in exon 6 of the NBS1 gene, resulting in a
frameshift and a truncated protein. The deletion introduced a premature
termination signal at codon 218, which was predicted to result in a
severely truncated polypeptide. The truncating 5-bp deletion (657del5)
had been identified in 90% of NBS patients. |
| Remarks |
Clinically affected; birth weight 5 lbs 6 oz; microcephaly and poor growth noted in first 3 months of life; short stature; developmental delay; hypogammaglobulinemia diagnosed at age 6; at age 18 height was 129 cm, weight was 22.6 kg and, head circumference was 42 cm; birdlike facies with a prominent beaked nose and recessed chin; low-set ears; hypoplasia of dental enamel; tympanic membranes appeared scarred; small tonsils; no cervical lymphoid tissue palpable; bilateral rales on chest exam; severe immunodeficiency; lymphopenic with decreases in both B and T cell numbers; proliferative responses to mitogens were poor; serum IgG 120 mg/dL; IgM 20 mg/dL; IgA undetectable; high incidence of chromosome breakage; T cells show breakage at fragile sites on chromosomes 7 and 14; donor subject is homozygous for a deletion of 5 nucleotides in exon 6 of the NBS1 gene, resulting in a frameshift and a premature termination at codon 218 [657-661delACAAA (657del5)]; mother is GM08037; father is GM08036; see GM07078 lymphocyte cell line. |
| Salewsky B, Wessendorf P, Hirsch D, Krenzlin H, Digweed M, Nijmegen Breakage Syndrome: The clearance pathway for mutant nibrin protein is allele specific Gene: 2013 |
| PubMed ID: 23458873 |
| |
| Hada M, Huff JL, Patel ZS, Kawata T, Pluth JM, George KA, Cucinotta FA, AT cells are not radiosensitive for simple chromosomal exchanges at low dose Mutation research716:76-83 2011 |
| PubMed ID: 21889946 |
| |
| 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 |
| |
| Yuan Z, Zhang X, Sengupta N, Lane WS, Seto E, SIRT1 regulates the function of the Nijmegen breakage syndrome protein Molecular cell27:149-62 2006 |
| PubMed ID: 17612497 |
| |
| Al Rashid ST, Dellaire G, Cuddihy A, Jalali F, Vaid M, Coackley C, Folkard M, Xu Y, Chen BP, Chen DJ, Lilge L, Prise KM, Bazett Jones DP, Bristow RG, Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo Cancer research65:10810-21 2005 |
| PubMed ID: 16322227 |
| |
| Alt JR, Bouska A, Fernandez MR, Cerny RL, Xiao H, Eischen CM, Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J Biol Chem280(19):18771-81 2005 |
| PubMed ID: 15734743 |
| |
| Araujo FD, Stracker TH, Carson CT, Lee DV, Weitzman MD, Adenovirus type 5 E4orf3 protein targets the Mre11 complex to cytoplasmic aggresomes Journal of virology79:11382-91 2005 |
| PubMed ID: 16103189 |
| |
| Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM, A patient with mutations in DNA Ligase IV: Clinical features and overlap with Nijmegen breakage syndrome. Am J Med Genet A137(3):283-7 2005 |
| PubMed ID: 16088910 |
| |
| 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 |
| |
| Rogoff HA, Pickering MT, Frame FM, Debatis ME, Sanchez Y, Jones S, Kowalik TF, Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm/Nbs1/Chk2. Mol Cell Biol24(7):2968-77 2004 |
| PubMed ID: 15024084 |
| |
| Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston D, SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. Genes Dev18(11):1305-16 2004 |
| PubMed ID: 15175262 |
| |
| Davalos AR, Campisi J, Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks. J Cell Biol162(7):1197-209 2003 |
| PubMed ID: 14517203 |
| |
| Eller MS, Li GZ, Firoozabadi R, Puri N, Gilchrest BA, Induction of a p95/Nbs1-mediated S phase checkpoint by telomere 3' overhang
specific DNA. FASEB J17(2):152-62 2003 |
| PubMed ID: 12554694 |
| |
| Kim JS, Krasieva TB, LaMorte V, Taylor AM, Yokomori K, Specific recruitment of human cohesin to laser-induced DNA damage. J Biol Chem277(47):45149-53 2002 |
| PubMed ID: 12228239 |
| |
| Yazdi PT, Wang Y, Zhao S, Patel N, Lee EY, Qin J, SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev16(5):571-82 2002 |
| PubMed ID: 11877377 |
| |
| Buscemi G, Savio C, Zannini L, Micciche F, Masnada D, Nakanishi M, Tauchi H, Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, Delia D, Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol21(15):5214-22 2001 |
| PubMed ID: 11438675 |
| |
| Lombard DB, Guarente L, Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and
meiotic telomeres. Cancer Res60(9):2331-4 2000 |
| PubMed ID: 10811102 |
| |
| Wu X, Ranganathan V, Weisman DS, Heine WF, Ciccone DN, O'Neill TB, Crick KE,
Pierce KA, Lane WS, Rathbun G, Livingston DM, Weaver DT, ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA
damage response. Nature405(6785):477-82 2000 |
| PubMed ID: 10839545 |
| |
| Curry CJ, O'Lague P, Tsai J, Hutchison HT, Jaspers NG, Wara D, Gatti RA, Hutchinson HT$[corrected to Hutchison HT], ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome [published erratum appears in Am J Hum Genet 1989 Oct;45(4):663] Am J Hum Genet45:270-5 1989 |
| PubMed ID: 2491181 |
| |
| Jaspers NG, Gatti RA, Baan C, Linssen PC, Bootsma D, Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients. Cytogenet Cell Genet49:259-63 1988 |
| PubMed ID: 3248383 |
| |
| Jaspers NG, Taalman RD, Baan C, Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia. Am J Hum Genet42:66-73 1988 |
| PubMed ID: 3337113 |
| |
| Wegner RD, Metzger M, Hanefeld F, Jaspers NG, Baan C, Magdorf K, Kunze J, Sperling K, A new chromosomal instability disorder confirmed by complementation studies. Clin Genet33:20-32 1988 |
| PubMed ID: 3277755 |
| |
| Conley ME, Spinner NB, Emanuel BS, Nowell PC, Nichols WW, A chromosomal breakage syndrome with profound immunodeficiency. Blood67:1251-6 1986 |
| PubMed ID: 2421804 |
| |
| Nove J, Little JB, Mayer PJ, Troilo P, Nichols WW, Hypersensitivity of cells from a new chromosomal-breakage syndrome to DNA-damaging agents. Mutat Res163:255-62 1986 |
| PubMed ID: 3785261 |
| |
| Spinner, Immunodeficiency, microcephaly, and chromosome instability with multiple 7,14 rearrangements. Am J Hum Genet37:A118 (1985):255-62 1985 |
| PubMed ID: 3785261 |
| Cumulative PDL at Freeze |
17.65 |
| Passage Frozen |
10 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
|