GM15989
Fibroblast from Skin, Unspecified
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 |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Simian Virus 40
|
|
Sample Source
|
Fibroblast from Skin, Unspecified
|
|
Race
|
White
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| 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 |
The SV40 Transformed precrisis derivative of GM07166, a skin fibroblast strain established from a child diagnosed initially as having severe combined immunodeficiency and chromosome breakage syndrome (Conley et al, Blood 67:1251-1256,1986) later distinguished as genetically separate from ataxia-telangiectasia (Wegner et al, Clinical Genetics 33:20-32,1988; Jasper et al, Am J Hum Genet 42:66-73,1988), but showing similar x-ray sensitivity to ataxia telangiectasia (Jaspers et al, Cytogenet Cell Genet 49:259-263,1988); in 1998 GM07166 was identified as Nijmegen breakage syndrome carrying the Slavic mutation: deletion of 5bp at nucleotide 657 in exon 6 of the NBS1 gene resulting in premature termination at codon 218 [657-661delACAAA (657del5)] (Vason et al, Cell 93:467-476,1998); the chromosome counts vary from near diploid to near triploid to near tetraploid; the number of structural chromosome aberrations varies from 2 per cell in the near diploids to 17 per cell in the near tetraploids; it is not clear that any of the marker chromosomes recur in any of the cells; massive numbers of aberrations that are not clonal cannot be dealt with by the ISCN; it is to be expected that an SV40 transformant of a cell line from a donor with a chromosome instability syndrome is unstable with respect to both chromosome number and structural integrity |
| Rossi R, Lidonnici MR, Soza S, Biamonti G, Montecucco A, The dispersal of replication proteins after Etoposide treatment requires the cooperation of Nbs1 with the ataxia telangiectasia Rad3-related/Chk1 pathway. Cancer Res66(3):1675-83 2006 |
| PubMed ID: 16452227 |
| |
| Furuta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA, Pilch DR,
Rogakou EP, Celeste A, Chen HT, Nussenzweig A, Aladjem MI, Bonner WM, Pommier Y, Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in
response to replication-dependent DNA double-strand breaks induced by mammalian
DNA topoisomerase I cleavage complexes. J Biol Chem278(22):20303-12 2003 |
| PubMed ID: 12660252 |
| |
| Weiss RS, Leder P, Vaziri C, Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Mol Cell Biol23(3):791-803 2003 |
| PubMed ID: 12529385 |
| Split Ratio |
1:7 |
| 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 |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
|
|