Cystic fibrosis is an inherited disorder that affects cells throughout the body, with its most noticeable impact on the respiratory and digestive systems. The condition arises from a problem within the body’s genetic code, which disrupts normal organ function and explains why it is a lifelong condition.
The Genetic Location of Cystic Fibrosis
The body’s genetic instructions are packaged into 23 pairs of chromosomes. The gene altered in cystic fibrosis is located on Chromosome 7. More precisely, it resides on the long arm of this chromosome at a position designated 7q31.2.
This gene is known as the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. A gene is a segment of DNA that provides the blueprint for making a specific protein. It is within the CFTR gene on Chromosome 7 that mutations occur, giving rise to the disease.
The Normal Function of the CFTR Gene
The CFTR gene holds the instructions for building the CFTR protein. This protein acts as a channel on the surface of epithelial cells, which line the passageways of organs like the lungs and pancreas. The primary job of the CFTR protein channel is to transport chloride ions, a component of salt, across the cell membrane. This movement of chloride regulates the balance of salt and water.
This regulation controls the consistency of mucus. By allowing chloride ions to exit cells, the CFTR protein helps draw water into the mucus, keeping it thin and slippery. This allows the mucus to move freely, removing trapped dust and germs from the airways and letting digestive enzymes flow from the pancreas.
How a Gene Mutation Causes Disease Symptoms
Mutations in the CFTR gene disrupt the production and function of the CFTR protein. Over 2,500 different mutations have been identified, but the most common, F508del, involves the deletion of three DNA base pairs. This error results in a misfolded, non-functional protein that does not reach the cell surface. As a result, the chloride ion channel is either absent or defective.
Without a working channel, chloride ions become trapped inside the cells. This imbalance disrupts the normal flow of water, causing the mucus on the outside of the cells to become abnormally thick and sticky. This mucus then clogs pathways throughout the body, causing the main symptoms of cystic fibrosis.
In the lungs, this thick mucus obstructs airways, making breathing difficult and trapping bacteria, leading to chronic infections. In the pancreas, sticky secretions block ducts, preventing digestive enzymes from reaching the small intestine, which impairs nutrient absorption. This same process affects other organs, including the sweat glands, where faulty salt transport results in abnormally salty sweat.
Inheritance Pattern and Genetic Identification
Cystic fibrosis is passed down in a pattern known as autosomal recessive inheritance. For a child to develop the condition, they must inherit two mutated copies of the CFTR gene—one from each parent. The parents are carriers, meaning they have one normal and one mutated copy of the gene. Carriers do not have symptoms because their single functional gene produces enough CFTR protein to prevent the disease.
When two carriers have a child, there is a 25% chance the child will inherit two mutated genes and have CF, a 50% chance the child will inherit one mutated gene and be a carrier, and a 25% chance the child will inherit two normal genes. This inheritance pattern is why the disease can appear in a family with no prior history of it.
The condition is often identified after birth through newborn screening programs that measure a pancreatic chemical in the blood. Diagnosis is confirmed with a sweat test, which detects elevated salt levels, or through genetic testing. Genetic tests analyze DNA to identify specific mutations in the CFTR gene, confirming a diagnosis or determining a person’s carrier status.