CFTR mutations are changes in the gene responsible for creating the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These genetic alterations can lead to a protein that is either missing, faulty, or produced in insufficient amounts. Such disruptions affect the body’s ability to properly regulate the movement of salt and water in and out of cells. This cellular imbalance ultimately impacts various organ systems throughout the body.
The CFTR Gene and Its Normal Function
The CFTR gene provides the blueprint for the CFTR protein, which acts as a channel across cell membranes. This protein’s primary role involves regulating the transport of negatively charged chloride ions and water across cell surfaces.
The normal function of the CFTR protein ensures that mucus, sweat, saliva, tears, and digestive enzymes have a thin, slippery consistency. For instance, in the lungs, the CFTR channel moves chloride ions out of cells, which then attracts water to the cell surface, creating a watery layer. This watery layer allows tiny hairs, called cilia, to effectively sweep mucus and debris away, keeping airways clear.
How CFTR Mutations Disrupt Cellular Processes
Mutations in the CFTR gene interfere with the proper production or function of the CFTR protein. Depending on the specific mutation, the resulting protein might be absent, reduced, or malformed, preventing chloride ion channels from opening correctly and disrupting the normal flow of chloride and water.
When chloride ions become trapped inside cells due to a defective CFTR protein, water is not drawn to the cell surface as it should be. This lack of hydration causes the mucus covering the cells to become unusually thick and sticky. This abnormally thick mucus can then clog various ducts and passageways throughout the body.
Impact on Body Systems
The systemic effects of disrupted CFTR function are widespread, primarily impacting organs that rely on thin, free-flowing secretions. The lungs are affected, as thick, sticky mucus obstructs airways, making breathing difficult. This mucus also creates a favorable environment for bacteria, leading to frequent and persistent lung infections, inflammation, and progressive lung damage.
The pancreas is also affected, as thick mucus blocks the ducts that release digestive enzymes. This blockage impairs the digestion and absorption of nutrients, particularly fats, leading to issues like fatty stools and malnutrition. Over time, this can cause damage to the pancreas itself.
Other organs can also experience issues due to CFTR mutations. The liver may develop blockages in its bile ducts, and the intestines can suffer from obstructions due to poorly hydrated stools. Additionally, sweat glands are affected; while sweat volume is normal, the reabsorption of salt is impaired, resulting in unusually salty sweat.
Inheritance and Detection of CFTR Mutations
CFTR mutations are inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a mutated CFTR gene—one from each parent—to develop the condition. If a person inherits only one mutated copy and one normal copy, they are considered a “carrier” and typically do not exhibit symptoms, but can pass the mutation to their children.
Newborn screening programs often detect CFTR mutations, typically through a blood test for elevated immunoreactive trypsinogen (IRT) levels. If positive, further diagnostic tests are performed. Genetic testing, usually done on blood, saliva, or cheek cells, identifies specific CFTR gene mutations. The sweat chloride test, considered a gold standard, measures the amount of chloride in sweat; elevated levels often indicate CFTR dysfunction.
Current Management Strategies
Current management strategies for CFTR mutations focus on alleviating symptoms and improving quality of life. Airway clearance techniques, such as chest physiotherapy and nebulized saline, help loosen and remove thick mucus from the lungs. Inhaled bronchodilators can relax airways, while antibiotics are used to treat or prevent lung infections.
Pancreatic enzyme replacement therapy is a common treatment to assist with digestion and nutrient absorption. A significant advancement in treatment includes CFTR modulator therapies, which are medications designed to target the underlying protein defect. These modulators work by improving the function of the defective CFTR protein, either by helping it fold correctly to reach the cell surface or by enhancing its activity once it is there.