Page title ‘Causes of CF’ with illustration on the right-hand side portraying a white microscope, a purple screen showing the DNA helix, and three stacked books of different colours

What is cystic fibrosis?

Cystic fibrosis is a genetic disease

Our bodies are made up of cells, and each cell contains around 20,000–25,000 genes.1,2 Genes are part of our DNA, the unique material inside all our cells that is the molecular code for everything in our bodies.2,3 They are a set of instructions that determine our individual characteristics, such as eye and hair colour.2,3

Genes contain the instructions for making proteins, which are the building blocks for everything in the body; they are very important for keeping our bodies working properly.2,3 Everyone inherits two copies of each gene: one from each parent.3

Illustration diagram of DNA helix structure and chromosome structure, with labels reading ‘DNA’, ‘Gene’, and ‘Eye colour’ and ‘Hair colour’ leading from marked gene areas to a human figure

Sometimes, a gene might have a change in it that causes it to behave differently to a normal gene. This change is called a mutation.3,4
Cystic fibrosis (CF) is a disease people are born with. It is a genetic disease, meaning it is inherited from your parents.3,5

 

The CFTR gene

One of the genes in our bodies is called the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Everyone inherits two copies of this gene, which contains the instructions for making the CFTR protein.3 If one of the CFTR genes you inherit has a mutation that causes CF, this means you are a “carrier” of the mutated gene, but you do not have CF.3 If both CFTR genes you inherit have a mutation that causes CF, you are born with CF.3

 

Illustration diagram of the way CFTR mutations are inherited: two parent figure who are carriers of CF and four child figures (one with both mutation copies that has CF, two as carriers of CFTR, and one that does not have the mutation)

Figure adapted from Orenstein DM. 20123

As illustrated in the diagram above, if both parents are carriers of the mutated CFTR gene, each of their children has a 25% chance of having CF and a 50% chance of being a carrier.3

 

There are many different types of CFTR gene mutations

Not everyone with CF has the same mutations in their CFTR genes. We know of over 2000 different CFTR gene mutations.6 At least 401 of these cause CF, but most of them are extremely rare.7,8

People with CF can either have two copies of the same CFTR gene mutation (homozygous), or two different CFTR gene mutations (heterozygous).9 F508del is the most common CFTR gene mutation.8 Approximately 90% of people with CF in the UK have at least one copy of the F508del mutation.9 Other common mutations, for example R117H, G551D, G542X, 621+1G→T, 1717-1G→A, and N1303K, have a much lower prevalence.9

The type of CFTR gene mutations you have is called your “genotype”, and this is something your doctor should be able to tell you.3

 

    The cystic fibrosis transmembrane conductance regulator (CFTR) gene tells our cells how to make CFTR proteins.10 This gene provides the instructions that get passed to other parts of the cell in which the CFTR protein is made.10 Once CFTR proteins have been processed correctly inside the cell, they are transported to the cell surface (membrane).10

    What do CFTR proteins do?

    CFTR proteins are found on the surface of cells in many parts of the body, including the lungs, sweat glands, intestines, pancreas, sinuses and reproductive system.10 Here, they act like channels, with gates that open and close to control the flow of water and other particles, such as chloride ions (one of the key components that make up salt),in and out of cells.10,11

    Illustration of blue CFTR protein channels on a green cell surface; one channel is closed and four are open allowing chloride ions to move from the inside to the outside of cell

    Figure adapted from Orenstein DM. 20045

    Salt, water and mucus

    By controlling the flow of chloride ions in and out of cells, CFTR proteins help make sure that there is the right balance of salt and water in our organs. The correct balance of salt and water is needed to help keep mucus, a substance produced naturally by the body, thin and watery. Mucus covers and protects the lining of our airways, digestive system, reproductive system and other organs and tissues in the body.5

     

    If both CFTR genes you inherit from your parents have a mutation that causes CF, your body produces CFTR proteins that don’t work properly.3,5

    Different CFTR mutations can have different effects on CFTR proteins, even though the effects on the body can be very similar.5

    CFTR mutations and their effects on CFTR proteins

    1. Some mutations lead to decreased numbers of CFTR proteins at the cell surface (reduced quantity). The F508del mutation, the most common CFTR mutation worldwide, causes fewer CFTR protein channels on the cell surface.12

       

      Illustration of one blue open CFTR protein channel on a green cell surface, indicating reduced quantity of channels due to CFTR mutations

      Figure adapted from Orenstein DM. 20045

    2. Other mutations lead to CFTR proteins that don’t work correctly on the cell surface (reduced function). When CFTR proteins don’t work correctly, the channels on the cell surface don’t stay open for as long or as often as a functioning CFTR protein channel does.5,12

      Illustration of blue CFTR protein channels and light blue deformed CFTR protein channels on a green cell surface, indicating reduced function of channels due to CFTR mutations

      Figure adapted from Orenstein DM. 20045

    3. Finally, some mutations can lead to a reduction in both the quantity and the function of CFTR proteins.

      Illustration of one blue CFTR protein channel and one light blue deformed CFTR protein channel on a green cell surface, indicating reduced quantity and function of channels due to CFTR mutations

    What does reduced quantity and/or function of CFTR proteins mean?

    Having too few CFTR proteins at the cell surface and/or CFTR proteins that don’t work correctly means that water and other particles, such as chloride ions, cannot move freely in and out of your cells.5,12

    The result is that the balance of salt and water in your organs is no longer correct, which can cause your mucus to become thick and sticky. Thick and sticky mucus stops your organs (lungs and other parts of the body) from working properly and leads to the symptoms of CF.5

      1. Orenstein DM. Ch.11: Genetics. Cystic Fibrosis: A Guide for Patient and Family. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012.

      2. Orenstein DM. Cystic Fibrosis: A Guide for Patient and Family. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.

      3. CFTR2 2022. Clinical and Functional Translation of CFTR. Helpful Information about CF and CFTR2. Available at: https://cftr2.org/resources. Accessed September 2023.

      4. Castellani C et al. J Cyst Fibros 2008;7(3):179 ̶ 196.

      5. MacDonald K et al. Pediatr Drugs 2007;9(1):1–10.

      6. Wang W et al. Biochim Biophys Acta 2012;1818(3):851–860.

      7. Welsh M et al. Cell 1993;73:1251–1254.

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