a Department of Medical Genetics, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
b Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Science , Tehran , Iran.
Expert Rev Clin Immunol. 2017 Dec;13(12):1155-1172. doi: 10.1080/1744666X.2017.1392856. Epub 2017 Oct 20.
Ataxia-telangiectasia (A-T) a multisystem disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. Identification of the gene defective in this syndrome, ataxia-telangiectasia mutated gene (ATM), and further characterization of the disorder together with a greater insight into the function of the ATM protein have expanded our knowledge about the molecular pathogenesis of this disease. Area covered: In this review, we have attempted to summarize the different roles of ATM signaling that have provided new insights into the diverse clinical phenotypes exhibited by A-T patients. Expert commentary: ATM, in addition to DNA repair response, is involved in many cytoplasmic roles that explain diverse phenotypes of A-T patients. It seems accumulation of DNA damage, persistent DNA damage response signaling, and chronic oxidative stress are the main players in the pathogenesis of this disease.
共济失调毛细血管扩张症（A-T）是一种多系统疾病，主要表现为小脑退行性变、毛细血管扩张、免疫缺陷、癌症易感性和辐射敏感性。该综合征中缺陷基因的鉴定，即共济失调毛细血管扩张症突变基因（ATM），以及对该疾病的进一步特征描述和对 ATM 蛋白功能的更深入了解，扩展了我们对这种疾病分子发病机制的认识。
在这篇综述中，我们试图总结 ATM 信号转导的不同作用，这些作用为 A-T 患者表现出的不同临床表型提供了新的见解。
除了 DNA 修复反应外，ATM 还参与许多细胞质作用，这些作用解释了 A-T 患者的多种表型。似乎是 DNA 损伤的积累、持续的 DNA 损伤反应信号和慢性氧化应激是这种疾病发病机制的主要因素。
