Cystic fibrosis is caused by mutations in a single gene called CFTR, which provides instructions for building a protein that moves salt and water across cell surfaces. When this gene is faulty, the protein either doesn’t work properly or isn’t produced at all, leading to thick, sticky mucus that clogs the lungs, pancreas, and other organs. More than 2,000 different mutations in the CFTR gene have been identified, but one specific mutation accounts for the vast majority of cases.
The Gene Behind Cystic Fibrosis
The CFTR gene sits on chromosome 7 and encodes a protein that acts as a channel on the surface of cells lining the lungs, digestive tract, sweat glands, and reproductive organs. This channel controls the flow of chloride (a component of salt) and bicarbonate in and out of cells. When the gene carries a mutation, the channel either never forms, forms but gets destroyed before reaching the cell surface, or reaches the surface but doesn’t open and close correctly.
The single most common mutation is called F508del, found in roughly 90% of people with cystic fibrosis (about half carry two copies of it). This mutation causes the protein to fold incorrectly inside the cell. The cell’s quality-control system recognizes the misfolded protein as defective and breaks it down before it ever reaches the surface, so the chloride channel is essentially absent.
Other mutations disrupt the process at different points. Some prevent the gene from producing a complete protein at all. Others allow the protein to reach the cell surface but leave the channel stuck closed, or open it but with reduced flow. Still others produce a normal protein that simply doesn’t last long enough at the surface before the cell pulls it back in and recycles it. The type of mutation influences how much residual protein function a person retains, which partly explains why severity varies so widely between individuals.
How a Faulty Channel Creates Thick Mucus
In healthy airways, the CFTR channel does two things simultaneously: it pushes chloride out of the cell onto the surface, and it puts the brakes on a neighboring channel that pulls sodium back in. These two actions work together to maintain a thin layer of liquid on the surface of the airways, keeping mucus hydrated and easy to clear.
When CFTR is missing or broken, chloride can’t get out and sodium absorption runs unchecked. The salt imbalance draws water out of the surface liquid and back into the cells through tiny water channels. The result is a dramatically dehydrated airway surface. Mucus that would normally glide along on a watery layer instead becomes thick and sticky, clogging small airways and trapping bacteria.
What Happens in the Lungs
The lungs of a baby with cystic fibrosis are actually normal at birth. Damage develops over time as the dehydrated mucus plugs small airways and creates pockets where bacteria can thrive. The immune system responds with aggressive inflammation, sending waves of white blood cells that release chemicals intended to fight infection but that also damage lung tissue.
This sets up a destructive cycle. Inflammation triggers cells to produce even more mucus, which traps more bacteria, which drives more inflammation. Over time, the walls of the airways weaken and stretch permanently, a condition called bronchiectasis. The progressive scarring and obstruction eventually impairs the lungs’ ability to exchange oxygen and carbon dioxide. Lung disease remains the leading cause of death in people with cystic fibrosis.
Effects on the Pancreas and Digestion
The same thick secretions that clog the lungs also block the tiny ducts of the pancreas. Normally, the pancreas releases digestive enzymes into the small intestine after a meal to break down fats, proteins, and carbohydrates. In cystic fibrosis, those enzymes get trapped. Without them reaching the intestine, food passes through largely undigested, leading to greasy, foul-smelling stools, cramping abdominal pain, and poor absorption of nutrients and fat-soluble vitamins.
The trapped enzymes can also begin digesting the pancreas itself, causing inflammation. In severe or long-standing cases, this damage extends to the insulin-producing cells of the pancreas, and the person develops a form of diabetes specific to cystic fibrosis. Roughly 40 to 50% of adults with CF eventually develop this complication.
How Cystic Fibrosis Is Inherited
Cystic fibrosis follows an autosomal recessive pattern, meaning a child must inherit a defective copy of the CFTR gene from each parent to develop the disease. People who carry one defective copy and one working copy are called carriers. They have no symptoms and typically don’t know they carry the gene.
When two carriers have a child, there is a 25% chance the child inherits both defective copies and has cystic fibrosis, a 50% chance the child inherits one defective copy and becomes a carrier, and a 25% chance the child inherits two working copies. These odds apply independently to each pregnancy.
Carrier rates vary by ethnic background. In populations of European descent, approximately 1 in 28 to 1 in 40 people carry a CFTR mutation. The disease occurs in about 1 in 3,000 to 1 in 6,000 live births in these populations. Incidence varies strikingly even within Europe, from as high as 1 in 1,353 births in Ireland to as low as 1 in 25,000 in Finland. In the United States, the overall rate is roughly 1 in 4,000 births, with significant variation across racial and ethnic groups.
How It’s Detected
Most countries with large populations of European descent now screen newborns for cystic fibrosis within the first week of life using a heel-prick blood test. The test measures a substance called immunoreactive trypsinogen, a pancreatic enzyme that leaks into the blood at elevated levels when the pancreatic ducts are blocked. Babies with high levels are either retested a few weeks later or have their blood sample analyzed for common CFTR mutations, depending on the screening protocol used in their region.
A positive screen leads to a sweat test, which remains the gold standard for diagnosis. The test measures the concentration of chloride in sweat, since faulty CFTR channels in sweat glands cause abnormally salty sweat. A chloride level of 60 mmol/L or higher confirms the diagnosis. Values between 30 and 59 mmol/L fall into an intermediate range that warrants genetic testing to look directly for CFTR mutations. Values below 30 mmol/L are considered normal.
Genetic testing can also identify the specific mutations a person carries, which has become increasingly important because newer treatments called CFTR modulators work by targeting specific types of protein defects. Knowing whether the protein is absent, misfolded, or present but malfunctioning helps determine which therapies are likely to be effective.