Description:
NIJMEGEN BREAKAGE SYNDROME
NIJMEGEN BREAKAGE SYNDROME GENE; NBS1
MARKER CHROMOSOME
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
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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ISCN
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46,XX,21ps+
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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 |
| |
| 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 GM07166 fibroblast cell line. |
| Yehezkel S, Segev Y, Viegas-Péquignot E, Skorecki K, Selig S, Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions Human molecular genetics: 2008 |
| PubMed ID: 18558631 |
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| 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 |
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| 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 |
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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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| Buscemi G, Perego P, Carenini N, Nakanishi M, Chessa L, Chen J, Khanna K, Delia D, Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks Oncogene23:7691-700 2004 |
| PubMed ID: 15361830 |
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| Delia D, Piane M, Buscemi G, Savio C, Palmeri S, Lulli P, Carlessi L, Fontanella E, Chessa L, MRE11 mutations and impaired ATM-dependent responses in an Italian family with Ataxia-Telangiectasia Like Disorder (ATLD). Hum Mol GenetEpub ahead of print:7691-700 2004 |
| PubMed ID: 15269180 |
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| 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 |
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| Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L,
Morgan WF, Petrini JH, The hMre11/hRad50 protein complex and Nijmegen
breakage syndrome: linkage of double-strand break repair to the cellular
DNA damage response. Cell93(3):477-86 1998 |
| PubMed ID: 9590181 |
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| Conley ME, Spinner NB, Emanuel BS, Nowell PC, Nichols WW, A chromosomal breakage syndrome with profound immunodeficiency. Blood67:1251-6 1986 |
| PubMed ID: 2421804 |
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| Spinner, Immunodeficiency, microcephaly, and chromosome instability with multiple 7,14 rearrangements. Am J Hum Genet37:A118 (1985):1251-6 1985 |
| PubMed ID: 2421804 |
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