A CFTR gene mutation represents an alteration in the genetic instructions within a person’s cells. Genes serve as blueprints for producing various proteins, which perform specialized functions throughout the body. A mutation means the gene’s code is different from its typical sequence.
The Role of the Normal CFTR Gene
The normal CFTR gene provides instructions for creating the CF transmembrane conductance regulator protein. This protein acts as a channel embedded in the membranes of cells that produce substances like mucus, sweat, saliva, tears, and digestive enzymes. Its main function involves transporting chloride ions across cell membranes, moving them both into and out of the cell. This movement of chloride ions helps regulate the flow of water in tissues. Maintaining this balance of salt and water is necessary for the body to produce thin, freely flowing mucus. Mucus lubricates and protects the lining of various systems, including the airways, digestive system, and reproductive system. The CFTR protein also influences the function of other channels, such as those that transport sodium ions across cell membranes, supporting the proper operation of organs like the lungs and pancreas.
How a Mutation Causes Dysfunction
A mutation in the CFTR gene is comparable to a typographical error in these genetic instructions. This “typo” leads to a faulty CFTR protein that cannot perform its job. The resulting protein might be the wrong shape, unable to fold correctly, or degraded quickly within the cell before it can reach the cell surface.
For instance, the common F508del mutation results in a misfolded protein that the cell recognizes as abnormal and quickly removes, preventing it from becoming a functional channel. When the CFTR protein is faulty, it fails to properly transport chloride ions, disrupting the normal movement of water across cell surfaces. This imbalance causes the mucus that lines various bodily passages, such as those in the airways and digestive tract, to become abnormally thick and sticky.
The Link to Cystic Fibrosis
Mutations in the CFTR gene are responsible for cystic fibrosis (CF), a genetic disorder. The characteristic thick, sticky mucus, a direct result of the faulty CFTR protein, clogs passages within multiple organs throughout the body. This obstruction leads to various health complications.
In the lungs, this dense mucus obstructs the airways, making breathing difficult and trapping bacteria. This stagnant environment promotes recurrent infections and inflammation, which can progressively damage lung tissue. The pancreas is also affected, as the thick mucus blocks the ducts that release digestive enzymes into the small intestine. This blockage leads to pancreatic insufficiency, impairing the body’s ability to properly digest food and absorb nutrients, often resulting in poor growth and fatty stools.
Classes of CFTR Mutations
Over 2,000 identified CFTR gene mutations are categorized into several classes based on how they affect the CFTR protein’s production or function. The specific class of mutation can influence how severely the condition manifests and may guide the selection of targeted treatments.
- Class I mutations lead to no CFTR protein being produced at all, often because of an early “stop” signal in the genetic code.
- Class II mutations, which include the common F508del, result in a protein that is made but misfolds and is rapidly degraded before it can reach the cell membrane.
- Class III mutations allow the protein to reach the cell surface, but the channel’s “gate” does not open properly, preventing ion flow.
- Class IV mutations, the protein reaches the surface and opens, but the movement of ions through the channel is significantly reduced.
- Class V mutations result in a reduced quantity of normal CFTR protein being produced.
- Class VI mutations involve a protein that functions but degrades too quickly.
Inheritance and Genetic Testing
Cystic fibrosis follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of a mutated CFTR gene—one from each biological parent—to develop the condition. If a person inherits only one mutated copy and one normal copy, they are considered a carrier of the CFTR gene mutation.
Carriers do not exhibit symptoms but can pass the mutated gene to their offspring. Genetic testing is available to identify CFTR gene mutations, playing a role in newborn screening programs where a blood test can indicate the need for further DNA analysis. Carrier screening is also offered to individuals or couples planning a pregnancy, and diagnostic testing can be performed for those presenting with symptoms.