Nijmegen breakage syndrome
| Nijmegen breakage syndrome | |
|---|---|
| Classification and external resources | |
| OMIM | 251260 |
| DiseasesDB | 32395 |
| eMedicine | derm/725 |
| MeSH | D049932 |
Nijmegen breakage syndrome (NBS), also known as Berlin breakage syndrome and Seemanova syndrome, is a rare autosomal recessive[1] congenital disorder causing chromosomal instability, probably as a result of a defect in the Double Holliday junction DNA repair mechanism.
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...)
The name derives from the Dutch city Nijmegen where the condition was first described.[2]
Most people with NBS have West Slavic origins. The largest number of them live in Poland.
Mrs Seemanova MD after whom the name of the syndrome was given, currently works at Motol Hospital, Prague, Czech Republic, as a Professor of medical genetics.
Characteristics
It is characterized by microcephaly, a distinct facial appearance, short stature, immunodeficiency, radiation sensitivity and a strong predisposition to lymphoid malignancy.[3][4]
Cause and Genetics
NBS is caused by a mutation in the NBS1 gene, located at human chromosome 8q21.[5][6] The disease is inherited in an autosomal recessive manner.[1] 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.
References
- ↑ 1.0 1.1 Cheung, V. G.; Ewens, W. J. (August 2006). "Heterozygous carriers of Nijmegen Breakage Syndrome have a distinct gene expression phenotype". Genome Research (Free full text) 16 (8): 973–979. doi:10.1101/gr.5320706. PMC 1524869. PMID 16809669.
- ↑ Weemaes CM, Hustinx TW, Scheres JM, van Munster PJ, Bakkeren JA, Taalman RD. (1981). "A new chromosomal instability disorder: the Nijmegen breakage syndrome". Acta Paediatr Scand 70 (4): 557–64. doi:10.1111/j.1651-2227.1981.tb05740.x. PMID 7315300.
- ↑ Digweed M, Sperling K (2004). "Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks". DNA Repair (Amst) 3 (8-9): 1207–17. doi:10.1016/j.dnarep.2004.03.004. PMID 15279809.
- ↑ "Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group". Arch Dis Child 82 (5): 400–6. 2000. PMC 1718318. PMID 10799436. Full text
- ↑ Iijima K, Komatsu K, Matsuura S, Tauchi H (2004). "The Nijmegen breakage syndrome gene and its role in genome stability". Chromosoma 113 (2): 53–61. doi:10.1007/s00412-004-0298-0. PMID 15258809.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 602667
External links
- nijmegen at NIH/UW GeneTests
- http://www.nijmegenbreakagesyndrome.net/homepage.htm
- Nijmegen Breakage Syndrome at NIH's Office of Rare Diseases
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