Ataxia‐telangiectasia: A review of clinical features and molecular pathology

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 cereb...

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Bibliographic Details
Published in:Pediatric allergy and immunology 2019-05, Vol.30 (3), p.277-288
Main Authors: Amirifar, Parisa, Ranjouri, Mohammad Reza, Yazdani, Reza, Abolhassani, Hassan, Aghamohammadi, Asghar
Format: Article
Language:English
Subjects:
Angiogenesis
Ataxia
ataxia‐telangiectasia
ATM
Cell cycle
Cell viability
Cerebellar ataxia
Cerebellum
Complications
Cytoplasm
DNA damage
double‐strand breaks repair
Heterogeneity
Immunodeficiency
Kinases
Medicin och hälsovetenskap
Metabolic disorders
Metabolism
Mitochondria
Mutation
Organelles
Oxidative stress
Peroxisomes
Primary immunodeficiencies
primary immunodeficiency
Protein kinase
Protein-serine/threonine kinase
Radiosensitivity
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Summary: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.
ISSN:0905-6157
1399-3038
1399-3038
DOI:10.1111/pai.13020