Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Molecular Medicine and Genetics Department, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Pediatr Allergy Immunol. 2019 May;30(3):277-288. doi: 10.1111/pai.13020. Epub 2019 Mar 20.
Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency (PID) disease that is caused by mutations in ataxia-telangiectasia mutated (ATM) gene encoding a serine/threonine protein kinase. A-T patients represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, susceptibility to malignancies, and increased metabolic diseases. This congenital disorder has phenotypic heterogeneity, and the severity of symptoms varies in different patients based on severity of mutations and disease progression. The principal role of nuclear ATM is the coordination of cellular signaling pathways in response to DNA double-strand breaks, oxidative stress, and cell cycle checkpoint. The pathogenesis of A-T is not limited to the role of ATM in the DNA damage response (DDR) pathway, and it has other functions mainly in the hematopoietic cells and neurons. ATM adjusts the functions of organelles such as mitochondria and peroxisomes and also regulates angiogenesis and glucose metabolisms. However, ATM has other functions in the cells (especially cell viability) that need further investigations. In this review, we described functions of ATM in the nucleus and cytoplasm, and also its association with some disorder formation such as neurologic, immunologic, vascular, pulmonary, metabolic, and dermatologic complications.
共济失调毛细血管扩张症（A-T）是一种常染色体隐性原发性免疫缺陷（PID）疾病，由编码丝氨酸/苏氨酸蛋白激酶的共济失调毛细血管扩张症突变（ATM）基因突变引起。A-T 患者表现出广泛的临床表现，包括进行性小脑共济失调、眼皮肤毛细血管扩张症、可变免疫缺陷、对辐射敏感、易发生恶性肿瘤和增加代谢疾病。这种先天性疾病具有表型异质性，不同患者的症状严重程度因突变的严重程度和疾病进展而异。核 ATM 的主要作用是协调细胞信号通路对 DNA 双链断裂、氧化应激和细胞周期检查点的反应。A-T 的发病机制不仅限于 ATM 在 DNA 损伤反应（DDR）途径中的作用，它在造血细胞和神经元中还有其他主要功能。ATM 调节线粒体和过氧化物酶体等细胞器的功能，也调节血管生成和葡萄糖代谢。然而，ATM 在细胞中（特别是细胞活力）还有其他功能，需要进一步研究。在这篇综述中，我们描述了 ATM 在细胞核和细胞质中的功能，以及它与一些疾病形成的关联，如神经、免疫、血管、肺、代谢和皮肤并发症。
