Nijmegen breakage syndrome
|Nijmegen breakage syndrome|
|Classification and external resources|
Nijmegen breakage syndrome (NBS), also known as Berlin breakage syndrome and Seemanova syndrome, is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the Double Holliday junction DNA repair mechanism and/or the Synthesis Dependent Strand Annealing mechanism for repairing double strand breaks in DNA (see Homologous recombination).
NBS1 codes for a protein that has two major functions: (1) to stop the cell cycle in the S phase, when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of DNA repair. This explains clearly that mutations in the NBS1 gene lead to higher levels of cancer (see Fanconi anemia, Cockayne syndrome...)
Cause and Genetics
NBS is caused by a mutation in the NBS1 gene, located at human chromosome 8q21. The disease is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Two adult siblings, both heterozygous for two particular NBS1 nonsense mutations displayed cellular sensitivity to radiation, chromosome instability and fertility defects, but not the developmental defects that are typically found in other NBS patients. These individuals appear to be primarily defective in homologous recombination, a process that accurately repairs double-strand breaks, both in somatic cells and during meiosis.
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- Online 'Mendelian Inheritance in Man' (OMIM) 602667
- Warcoin M, Lespinasse J, Despouy G, Dubois d'Enghien C, Laugé A, Portnoï MF, Christin-Maitre S, Stoppa-Lyonnet D, Stern MH (2009). "Fertility defects revealing germline biallelic nonsense NBN mutations". Hum. Mutat. 30 (3): 424–30. doi:10.1002/humu.20904. PMID 19105185.
- nijmegen at NIH/UW GeneTests
- Nijmegen Breakage Syndrome at NIH's Office of Rare Diseases