Cystic fibrosis causes

Last updated March 14, 2023, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD

Cystic fibrosis (CF) is caused by mutations in a gene called CFTR. These mutations are inherited from an individual’s biological parents, and they are present from the moment of conception.

What causes CF?

CF is caused by mutations in the CFTR gene, which provides cells with the instructions for building a protein, also called CFTR (short for cystic fibrosis transmembrane conductance regulator).

Normally, the CTFR protein is present on membranes of certain cells, where it acts like a gate, regulating the movement of certain salt molecules and water in and out of the cell. CFTR particularly regulates the movement of chloride ions, a type of negatively charged salt particle (the chloride component of sodium chloride or table salt). Measuring chloride content in sweat can be used for a CF diagnosis.

The movement of chloride and water is essential for the production of mucus. People with CF produce mucus that is unusually thick and sticky. This thick mucus builds up and causes damage to the body’s organs, particularly the lungs, pancreas, digestive tract, and reproductive system, which is mainly what causes the symptoms and signs of CF.

Types of CFTR mutations

According to the Johns Hopkins Cystic Fibrosis Center, more than 2,500 different mutations in the CFTR gene have been reported. There are different types of CFTR mutations with different effects on the CFTR protein, such as:

• preventing any protein from being made or reducing protein production
• trafficking defects, where the protein is not properly shuttled to the cell’s surface
• gating defects, where the gate-like CFTR protein cannot open normally
• decreasing protein stability so it degrades rapidly and cannot function properly.

All cases of CF lead to an inability to properly regulate the flow of chloride ions and water through the cell membrane, resulting in an abnormally thick and sticky mucus. Generally, CFTR mutations that cause more substantial problems with protein function tend to cause more severe disease.

Cystic fibrosis inheritance

As is the case with most genes, everyone has two copies of CFTR — one inherited from each biological parent. CF runs in families in an autosomal recessive pattern, which means that a person will develop CF only if both copies of CFTR are mutated.

Individuals who carry only one mutant copy of the gene do not develop CF, but they can pass the disease-causing gene to their biological children. As such, people with only one mutated copy of CFTR are known as carriers. 

If two carriers have biological children, there is a:

• 25% likelihood that the child will have CF
• 50% likelihood that the child will be a carrier but will not have CF
• 25% likelihood that the child will not be a carrier or have CF.

If someone with CF chooses to have biological children, that person is guaranteed to pass on one mutated copy of the CFTR gene to their child.

• If a person with CF has a child with someone who is not a carrier, then their child is guaranteed to be a carrier, but not have CF.
• If two people with CF have a child, their child is guaranteed to also have CF.

If a person with CF has a child with a CF carrier, there is a:

• 50% likelihood that the child will have CF
• 50% likelihood that the child will be a carrier but will not have CF.

How common are CF carriers?

Cystic fibrosis can affect people of all backgrounds, but CF-causing genetic mutations are more common in certain ethnic populations and groups. In the U.S., a study in 2011 based on more than 360,000 individuals referred for carrier testing estimated that the frequency of CF carriers is approximately:

• 1 out of every 25 to 30 Caucasian Americans and Ashkenazi Jewish Americans
• 1 out of every 60 to 85 African Americans
• 1 out of every 45 to 60 Hispanic Americans
• 1 out of every 70 Native Americans
• 1 out of every 90 Middle Eastern Americans
• 1 out of every 120 South Asian Americans.

While CF is always caused by mutations in the CFTR gene, certain specific disease-causing mutations are more common in certain ethnic groups than others. The specific mutation type can affect disease severity, and there are some CF treatments that only work for people with certain mutations.

Risk factors and disease progression

The mutations that cause cystic fibrosis are present in sperm and egg cells even before conception. The only true CF risk factor is having biological parents who have the disease or are known to be carriers.

For people who have CF, factors that can influence disease progression include:

• The type of mutation a person with CF has does influence the disease progression. In general, mutations that cause greater problems with the function of the CFTR protein (such as mutations that prevent any protein from being made at all) tend to be associated with more severe CF.
• Approved medications and other treatment options can help improve patients’ quality of life, ease symptoms, and slow the disease’s progression. For people with some underlying mutations, medicines called CFTR modulators can help to boost the function of the CFTR protein, which may ease CF symptoms and slow disease progression. Nondrug treatments like physical therapy, supplemental oxygen, and equipment to help clear mucus from the lungs also can help people with CF to maintain their health.
• People with CF are at increased risk of lung infections, particularly with the bacteria Pseudomonas aeruginosa. Chronic lung infections are a major driver of progressive lung damage in CF. Taking steps to avoid infections, such as regular handwashing and disinfecting surfaces, is generally recommended for people with CF.
• Due to nutritional problems as well as hormonal issues, children with CF often have impaired growth and tend to be shorter and lighter than typical for their age. Poor growth is a common early sign of CF and is a risk factor for worse lung disease and other clinical outcomes. Early interventions such as dietary modifications and hormone treatments may help to normalize growth for children with CF.
• Physical activity can help to improve lung function, boost cardiovascular fitness, and clear mucus from the lungs. It’s recommended that people with CF engage regularly in physical activity. Patients can work with their care team to come up with a physical fitness routine that works for them.
• Exposure to cigarette smoke can cause damage and irritation in the lungs, which can worsen CF lung disease. It’s recommended that people with CF avoid smoking and exposure to secondhand smoke.
• Liver problems in CF can mean that the liver has to work harder to clear alcohol from the body, so people with CF have a higher risk of alcohol-related liver damage than the general population. Alcohol also can alter blood sugar levels, which can cause problems for people with CF-related diabetes, and potentially interact with antibiotics and other medications.

Cystic Fibrosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.