Rare Diseases Genetic Disorders Causes and Risk Factors of Ataxia-Telangiectasia By Michelle Pugle Michelle Pugle Facebook LinkedIn Twitter Michelle Pugle is an expert health writer with nearly a decade of experience contributing accurate and accessible health information to authority publications. Learn about our editorial process Published on October 13, 2021 Medically reviewed by Jonathan B. Jassey, DO Medically reviewed by Jonathan B. Jassey, DO Facebook Jonathan Jassey, DO, is the founding pediatrician at Concierge Pediatrics in Long Island, New York. Learn about our Medical Expert Board Print Table of Contents View All Table of Contents Common Causes Genetics Lifestyle Risk Factors Ataxia-telangiectasia (A-T) is a rare type of genetic disease caused by a gene mutation known as ATM (ataxia-telangiectasia mutation). This means A-T is passed down from generation to generation. Your risk factors depend upon how many people in your family are carriers of the genetic mutation. This article discusses the genetic causes of A-T and associated risk factors. janiecbros / Getty Images Common Causes Genetic Mutation ATM gene mutations or changes interfere with healthy cell division and DNA strand maintenance and repair. ATM gene mutations are responsible for A-T syndrome. What Is a Genetic Mutation? A genetic mutation is a change in DNA sequence (the blocks that make up your DNA molecule). DNA molecules are located in the nucleus of cells. They carry your genetic fingerprint. Chronic Oxidative Stress Continuous oxidative stress is a feature of A-T in animal studies, but human clinical studies are still necessary. It can play a role in DNA damage, as well as cellular damage and carcinogenesis (when healthy cells turn cancerous). Researchers point to chronic oxidative stress as a factor in A-T and conditions similar to A-T, like Bloom syndrome and Nijmegen breakage syndrome. In A-T, the damage to nervous system cells contributes to the deterioration of voluntary movement. What Is Oxidative Stress? Chronic oxidative stress is when the body has an imbalance of free radicals and antioxidants. The free radicals can damage cell systems if antioxidants do not detoxify them. This can lead to disease if the damage is not repaired. Genetics A-T is known as an autosomal recessive disorder. This means these mutations have to be present on both copies of the gene (one copy from each biological parent) in order to cause A-T in offspring. If only one gene copy has the mutation, then the offspring becomes a carrier. Carriers usually do not show symptoms. The mutation is on the long arm (q) of chromosome 11 (11q22.3). Chromosomes are found in the nucleus of all body cells. If two carriers have a child, there is a 25% chance the child will develop A-T. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. Parents, siblings, and children of a person with A-T (i.e., first-degree relatives) have a 50% chance of inheriting the single gene mutation and becoming a carrier. ATM Mutation This genetic mutation encodes and gives the wrong instruction to a signaling protein (ataxia-telangiectasia mutated protein). When functioning, this protein fights DNA damage by releasing a different protein called p53 (tumor suppressor protein). It prevents cell division of unhealthy or damaged cells.With the ATM mutation, p53 protein doesn’t work nearly as well. Cells with damaged DNA can continue to divide, and some may be cancerous. This is why A-T is known as a hereditary cancer gene. Other names for the ATM gene include: AT mutatedAT proteinAT1ATAAtaxia-telangiectasia mutatedAtaxia-telangiectasia mutated (includes complementation groups A, C, and D)Ataxia-telangiectasia mutated proteinATCATDATDCATEATM_HUMANHuman phosphatidylinositol 3-kinase homologSerine-protein kinase ATMTEL1TELO1 Lifestyle Risk Factors Since A-T is an inherited genetic disease and symptoms often start in early childhood, lifestyle risk factors, or things you can change to lower your risk of developing a particular disease, aren’t applicable. But having A-T raises the risk of developing cancer. Reducing lifestyle risk factors for cancer is even more important for people with the condition and their family members. People with A-T have about a 40% risk of developing cancer, most likely leukemia or lymphoma. Those two cancers account for 85% of all cancers in people with A-T. People with A-T also have an increased risk of developing breast cancer, ovarian cancer, stomach cancer, skin cancer, and bone and soft tissue cancer. The American Cancer Society says being a carrier of the ATM gene (inheriting one abnormal copy of the gene) has been linked to a high rate of breast cancer in some families. A 2021 review study identified a specific mutation or ATM variant associated with increased breast cancer risk called the V2424G mutation. General risk factors for cancer include: Older ageA personal or family history of cancerUsing tobaccoObesityAlcoholSome types of viral infections, such as human papillomavirus (HPV)Specific chemicalsExposure to radiation, including ultraviolet radiation (UV) from the sun Summary Ataxia-telangiectasia is caused by an autosomal recessive gene mutation. Both genetic parents must pass the mutation to a child in order for the condition to develop. This gene normally works to keep damaged cells from dividing. With the mutation, damaged cells may continue to divide, raising the risk of cancer. A Word From Verywell If A-T runs in your family, you may be wondering if you’re a carrier. Genetic testing like carrier testing, predictive diagnosis, and genetic counseling can help determine your personal risk of passing down a genetic mutation or developing certain forms of cancer. Talk to your doctor about the pros and cons of genetic testing to see if it’s right for you. 7 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. American Society of Clinical Oncology. Ataxia-telangiectasia. Zaki-Dizaji M, Akrami SM, Abolhassani H, Rezaei N, Aghamohammadi A. Ataxia telangiectasia syndrome: moonlighting ATM. Expert Rev Clin Immunol. 2017;13(12):1155-1172. doi:10.1080/1744666X.2017.1392856 Maciejczyk M, Mikoluc B, Pietrucha B, et al. Oxidative stress: a concept in redox biology and medicine. Redox Biology. 2015;4:180-183. doi:10.1016/j.redox.2016.12.030 National Organization for Rare Disorders. Ataxia-telangiectasia. Cancer.net. Understanding cancer risk. American Cancer Society. Breast cancer risk factors you cannot change. Moslemi M, Moradi Y, Dehghanbanadaki H, et al. The association between ATM variants and risk of breast cancer: a systematic review and meta-analysis. BMC Cancer. 2021;21(1):27. doi:10.1186/s12885-020-07749-6 By Michelle Pugle Michelle Pugle, BA, MA, is an expert health writer with nearly a decade of contributing accurate and accessible health news and information to authority websites and print magazines. Her work focuses on lifestyle management, chronic illness, and mental health. Michelle is the author of Ana, Mia & Me: A Memoir From an Anorexic Teen Mind. 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