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FB2026_01
,
released March 12, 2026
This report describes ataxia-telangiectasia (AT), which exhibits autosomal recessive inheritance. The human gene implicated in this disease is ATM, which encodes the PI3/PI4-kinase ataxia-telangiectasia mutated; this kinase belongs to family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. There is a single fly ortholog, tefu, for which loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. ATM is also associated with the diseases somatic B-cell non-Hodgkin lymphoma, somatic mantle cell lymphoma, somatic T-cell prolymphocytic leukemia, and a susceptibility to breast cancer MIM:114480).
The human ATM gene has not been introduced into flies.
Animals homozygous for the more severe loss-of-function alleles of Dmel\tefu are semi-lethal; surviving adults exhibit rough eyes, notched wings, and shorter or missing bristles; females are sterile. Homozygous mutant neuroblast cells display severe mitotic abnormalities that are characterized by a high frequency of end-to-end fusions of chromosomes during mitosis, leading to the hypothesis that normal function of tefu is required to protect the linear ends of chromosomes. A mutation that results in reduction of kinase activity causes neuron and glial cell death in the adult brain and a reduction in mobility and longevity. ATM knockdown in glial cells, but not neurons, is sufficient to cause neuron and glial cell death, a reduction in mobility and longevity, and elevated expression of innate immune response genes in glial cells, indicating that a non-cell-autonomous mechanism contributes to the neurodegeneration and related phenotypes. Physical and genetic interactions of Dmel\tefu have been described; see below and in the gene report for tefu.
[updated Jul. 2020 by FlyBase; FBrf0222196]
[ATAXIA-TELANGIECTASIA; AT](https://omim.org/entry/208900)
[ATM SERINE/THREONINE KINASE; ATM](https://omim.org/entry/607585)
Classic ataxia-telangiectasia (A-T) is characterized by progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma. Individuals with A-T are unusually sensitive to ionizing radiation. Non-classic forms of A-T have included adult-onset A-T and A-T with early-onset dystonia. [from GeneReviews, Ataxia-Telangiectasia, pubmed:20301790 2016.02.08]
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases ("spider veins"), immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to killing by ionizing radiation (IR), and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The latter trait has been used to identify complementation groups for the classic form of the disease (Jaspers et al., 1988, pubmed:3248383). At least 4 of these (A, C, D, and E) map to chromosome 11q23 (Sanal et al., 1990, pubmed:2220826) and are associated with mutations in the ATM gene. [From MIM:615916, 2016.01.28]
Ataxia-telangiectasia (AT) is caused by homozygous or compound heterozygous mutation in the ATM gene. [From MIM:208900, 2016.01.29]
The cerebellum atrophies early in the course of classic A-T, being visibly smaller on MRI examination by age seven or eight years, with concomitant loss of Purkinje cells and depletion of granule cells [Sardanelli et al 1995, pubmed:7708196; Tavani et al 2003, pubmed:12740724; Lin et al 2006, pubmed:17177151; Wallis et al 2007 pubmed:17213429]. Microscopic nucleomegaly also occurs in the cells of tissues throughout the body. [from GeneReviews, Ataxia-Telangiectasia, pubmed:20301790 2016.02.08]
The ATM gene encodes ataxia-telangiectasia mutated, a protein that is a member of the phosphatidylinositol 3-kinase (see MIM:601232) family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control.[From MIM:607585, 2016.01.29]
One to one: 1 human to 1 Drosophila.
Ortholog of human ATM (1 Drosophila to 1 human).
Dmel\tefu shares 22% identity and 40% similarity with human ATM.