Ataxia telangiectasia pathophysiology
|
Ataxia telangiectasia Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Ataxia telangiectasia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Ataxia telangiectasia pathophysiology |
|
Risk calculators and risk factors for Ataxia telangiectasia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
The responsible gene in AT, ataxia-telangiectasia mutated (ATM), was discovered in 1995 by Savitsky et al.,[1] a team led by Yosef Shiloh of Tel Aviv University in Israel. Researchers linked the hyper-sensitivity of AT patients to ionizing radiation (IR) and predisposition to cancer, to "chromosomal instability, abnormalities in genetic recombination, and defective signaling to programmed cell death and several cell cycle checkpoints activated by DNA damage".[2] Earlier observations predicted that the gene altered in AT played a role in DNA damage recognition. These predictions were confirmed when a single gene on chromosome 11 (11q 22-23) was discovered.[1][3] Since its discovery, the protein product of the ATM gene has been shown to be a part of eukaryotic cell cycle control, DNA repair, and DNA recombination (Lavin, 2004). Specifically, the AT gene serves as a tumor suppressor gene by contributing to a network of genes that link double stranded breaks in DNA to cell cycle arrest and apoptosis (programmed cell death). Patients with ATM have a defective AT gene, which leaves them susceptible to contracting cancer. For example, female ATM patients have a two-fold higher chance of ever having breast cancer, which often occur before the age of 50. ATM patients must try avoiding x-rays at all costs since the radiation induces double-stranded breaks.
References
- ↑ 1.0 1.1 Savitsky K, Bar-Shira A, Gilad S; et al. (1995). "A single ataxia telangiectasia gene with a product similar to PI-3 kinase". Science. 268 (5218): 1749–53. doi:10.1126/science.7792600. PMID 7792600.
- ↑ Canman CE, Lim DS (1998). "The role of ATM in DNA damage responses and cancer". Oncogene. 17 (25): 3301–8. doi:10.1038/sj.onc.1202577. PMID 9916992.
- ↑ Gatti RA, Bick M, Tam CF; et al. (1982). "Ataxia-Telangiectasia: a multiparameter analysis of eight families". Clin. Immunol. Immunopathol. 23 (2): 501–16. doi:10.1016/0090-1229(82)90134-9. PMID 6213343.