Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasias, immune defects and a predisposition to malignancy. The birth frequency of AT is estimated to be about 1 in 100000–300000. The AT heterozygote frequency is estimated to be 0.5–1%. The patient shows progressive cerebellar ataxia since infancy. Telangiectasia typically develops after 3–5 years of age. Sixty to 80% of patients show immunodeficiency. Twenty to 30% of patients develop a malignancy, mainly leukemia or lymphoma. Laboratory finding shows decreased level of serum IgA, IgG2 and IgE. Increased level of serum α-fetoprotein is a specific feature. Peripheral circulating lymphocytes show characteristic intra-locus rearrangements involving T-cell receptor and/or immunoglobulin loci. Chromosomal breakage and hypersensitization to ionizing radiation (IR) are a hallmark cell biological feature of the AT cell. AT cells also show improper cell cycle regulation after IR, which has been known as radioresistant DNA synthesis.

The responsible gene, ataxia-telangiectasia mutated (ATM), contains 66 exons spanning approximately 150kb of genomic DNA at 11q22. 3. cDNA contains 10140bp. The ATM protein contains 3056 amino acids coded by a 9168-bp open reading frame. 1, 2 The ATM gene is also known to be mutated secondarily in various hematological malignancies, and is speculated to work as a tumor suppressor gene. 3 ATM protein is one of the members of phosphoinositide 3-kinase-related kinases. Exposure of cells to genotoxic stresses such as anticancer drugs or irradiation induces DNA double-strand breaks. The central player in such DNA damage response is ATM. 4 ATM