Our bodies are made of cells, each containing DNA, the instruction manual for life. DNA is organized into genes, which are blueprints for building and operating the body. A gene mutation is like a typo in these instructions, which can alter how a protein functions and lead to health issues. The ATM gene is one such gene involved in keeping our cells healthy and functioning correctly.
The Function of the ATM Gene
The ATM gene, which stands for Ataxia-Telangiectasia Mutated, provides instructions for making a protein that helps control the rate at which cells grow and divide. This protein acts as a first responder to DNA damage from factors like environmental exposures or natural cell division. The ATM protein is part of the cell’s surveillance system, detecting DNA double-strand breaks, which are serious and potentially harmful.
When the ATM protein detects a break in a DNA strand, it halts the cell’s division process, giving the cell time to repair the break accurately. It coordinates this repair by activating other proteins and enzymes that mend the broken DNA strands. This function ensures the genetic information remains stable and intact.
The ATM protein is a type of protein kinase, meaning it activates other proteins by adding a phosphate group to them, a process called phosphorylation. Once a DNA break is detected, ATM activates a cascade of signals involving more than a hundred different proteins in the repair network. This controlled process ensures damage is fixed before the cell divides again, preventing the accumulation of genetic errors.
Associated Health Conditions
When the ATM gene is mutated, its ability to manage DNA repair is compromised, leading to different health outcomes depending on the number of altered copies a person inherits. If an individual inherits two mutated copies, one from each parent, they develop a rare condition called Ataxia-Telangiectasia (A-T). This disorder appears in early childhood and is characterized by a combination of symptoms.
“Ataxia” refers to progressive difficulty with coordinating movements, often one of the first signs of the disorder. This loss of motor control is caused by the death of cells in the cerebellum, the part of the brain responsible for coordination. “Telangiectasia” describes the appearance of tiny, spider-like red veins on the whites of the eyes and the skin. Individuals with A-T also have a weakened immune system, making them highly susceptible to infections, and face a significantly increased risk of developing cancers like leukemia and lymphoma.
A different scenario arises when a person inherits only one mutated copy of the ATM gene, making them a carrier. Carriers do not have Ataxia-Telangiectasia, but the single non-functional gene copy means their cells have a reduced capacity to repair DNA damage effectively. This reduction elevates their lifetime risk for developing certain types of cancer.
The most well-documented risk for ATM carriers is an increased susceptibility to breast cancer, with studies suggesting the risk can be several times higher than the general population. The risk is not limited to breast cancer; carriers also face a higher likelihood of developing pancreatic cancer. There is also evidence linking the mutation to an increased risk for ovarian and prostate cancers.
Inheritance and Carrier Status
The inheritance pattern of the ATM gene mutation explains how both Ataxia-Telangiectasia (A-T) and carrier status are passed through families. A-T is classified as an autosomal recessive disorder. “Autosomal” means the gene is located on a numbered chromosome, not a sex chromosome, while “recessive” means a person must inherit two mutated copies to develop the condition.
A person who has one mutated copy of the ATM gene and one normal copy is a carrier. Carriers do not have the symptoms of A-T because the single functional gene is sufficient to produce enough ATM protein to prevent the disorder’s severe neurological and immunological problems. They can, however, pass the mutated gene on to their children.
The probabilities of inheritance can be understood when two carriers have a child. With each pregnancy, there is a 25% chance the child will inherit a mutated gene from both parents and have A-T. There is a 50% chance the child will inherit one mutated gene, becoming a carrier. Finally, there is a 25% chance the child will inherit two normal copies of the gene.
Genetic Testing and Medical Management
Genetic testing for ATM mutations is recommended for those with a personal or strong family history of Ataxia-Telangiectasia (A-T). It is also considered for individuals with a personal or family history of specific cancers, like breast or pancreatic cancer, particularly if diagnosed at an early age. The test itself requires only a blood or saliva sample, from which DNA is extracted and analyzed.
For confirmed ATM carriers, medical management focuses on proactive risk reduction and heightened cancer surveillance. For breast cancer risk, this often means starting screening at an earlier age and using more sensitive imaging, such as breast MRIs in addition to mammograms. Some individuals may also discuss risk-reducing medications or preventive surgeries with their healthcare providers.
For those diagnosed with A-T, management is supportive and aims to address the disorder’s symptoms. This includes physical and occupational therapy to help with movement challenges, prompt treatment of infections due to the weakened immune system, and regular cancer screenings. The goal is to manage symptoms and maintain the best possible quality of life.