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Ataxia Telangiectasia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
AT is an autosomal recessive disorder. Heterozygous parents harboring ATM pathogenic variant have a 25% chance of getting an affected offspring, who acquire biallelic (homozygous or compound heterozygous) mutations in the ATM gene; a 50% chance of getting a heterozygous carrier offspring, who is asymptomatic but at increased risk for breast cancer (especially in individuals with missense pathogenic variant) and coronary artery disease; and a 25% chance of getting an unaffected offspring. Affected individuals are often sterile with gonadal dysgenesis and do not reproduce.
Including Genetic Variables in NTCP Models Where Are We? Where Are We Going?
Published in Tiziana Rancati, Claudio Fiorino, Modelling Radiotherapy Side Effects, 2019
Sarah L. Kerns, Suhong Yu, Catharine M. L. West
The inclusion of genetic variables in NTCP models requires identifying sufficient variants to have a clinically useful test. It is the common variants that are of interest given rare variants such as homozygous mutations in the ATM gene can be associated with syndromes that are phenotypically obvious. Information on multiple SNPs can be combined to generate a polygenic risk score (Figure 19.2) to include in NTCP models. Work outside the radiotherapy field shows the potential. For example, analysis of ~89,000 prostate cancer cases and controls has identified >70 SNPs that account for ∼30% of the familial risk for the disease. The variants can be combined in a polygenic risk score, which shows a normal distribution. Men with a high-risk score at the top 1% of the risk distribution had a 4.7-fold increased risk for developing prostate cancer compared with the average of the population being profiled (Eeles 2013). Individuals with the highest burden of risk variants had a 30-fold increased risk of prostate cancer compared with those with the lowest polygenic risk scores.
Blood and immune system disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
This is a slow progressive disorder that afects the brain, causing an inability to coordinate muscle movements (ataxia). Ataxia telangiectasia is caused by a deficiency of the ataxia-telangiectasia-mutated (ATM) protein that plays a role in preventing the division of cells following damage to the DNA. If there is a deficiency of the protein the cells continue to divide and the DNA is not repaired. The ATM protein deficiency is caused by a defect in the ATM gene that is located on the long arm of chromosome 11.
Current perspectives on the diagnosis and management of acute transverse myelitis
Published in Expert Review of Neurotherapeutics, 2023
Nanthaya Tisavipat, Eoin P Flanagan
A recent epidemiologic study has shown that the prevalence of ATM in the US is 7.86 per 100,000 persons [3]. However, this prevalence includes ATM from all causes including multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neurosarcoidosis, paraneoplastic, infectious, and idiopathic. Careful evaluation could reveal a specific cause in up to 70% of patients referred for transverse myelitis [4,5]. Under the ATM umbrella, the pathophysiology differs by each specific etiology. Therefore, after the clinical syndrome of ATM is recognized, comprehensive clinical history, physical examination, and investigations should be pursued to reach a definitive diagnosis, which then determines the management strategy. This article focuses on the practical approach to narrow down the differential diagnoses and provides an update on the acute and long-term treatment for certain common causes of ATM.
ATM and TP53 polymorphisms modified susceptibility to radiation-induced lens opacity in natural high background radiation area, China
Published in International Journal of Radiation Biology, 2022
Yu Gao, Yin-Ping Su, Xiao-Liang Li, Shu-Jie Lei, Hui-Feng Chen, Shi-Yue Cui, Su-Fen Zhang, Jian-Ming Zou, Qing-Jie Liu, Quan-Fu Sun
ATM is a recognized radio-sensitive gene involved in DNA repair, mainly in double-strand breaks. Cells with mutant ATM lose the ability to cope with genotoxic stress due to lack of DNA damage response and loss of regulation of cell cycle. TP53 is one of the most important target involved in ATM-mediated DNA damage response, regulating the transcription of other genes responsible for DNA repair, growth arrest and apoptosis. Mice models have provided evidences that ATM and TP53 play important roles in radiation-induced and spontaneous cataract (Worgul et al. 2002; Wiley et al. 2011). Additionally, Hamada and Fujimichi (2015) has discussed the implications of DNA repair genes and tumor related factors (e.g., ATM, TP53) in radiation-induced cataractogenesis. However, few studies have been performed on the association between ATM and TP53 polymorphisms and radiation-induced opacity in humans.
Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management
Published in Expert Review of Clinical Immunology, 2020
Parisa Amirifar, Mohammad Reza Ranjouri, Martin Lavin, Hassan Abolhassani, Reza Yazdani, Asghar Aghamohammadi
One of the main symptoms of A-T patients is remarkably increased sensitivity to ionizing radiation (X-rays and gamma rays). This has also been demonstrated in a variety of A-T cells in culture. It seems the cause of increased sensitivity to ionizing radiation in A-T cells may be due to a defect in DNA damage response rather than a defect in DNA damage repair per se [119,120]. Generally, ATM protein has an important role in the early stages of a DNA damage-recognition pathway. In A-T cells, the regulation of cell-cycle responses is altered and decrease of checkpoint function after irradiation, allowing cells to continue cycling despite extensive DNA damage [121,122]. Radiation sensitivity measurement can be helpful for identification of cases with a higher risk of malignancy, a higher degree of immunodeficiency, and also cases that required adjustment of the cancer therapy [123,124].