2019 Jan 27. doi: 10.1111/pai.13020. [Epub ahead of print]

Ataxia-telangiectasia: A review of clinical features and molecular pathology.

Author information

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.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.


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 neurological, immunological, vascular, pulmonary, metabolic and dermatologic complications. This article is protected by copyright. All rights reserved.


ATM ; Ataxia telangiectasia; double strand breaks repair; primary immunodeficiency