Cystic fibrosis (CF) is a genetic condition, which means it is inherited. It is caused by a mutation in a single gene known as the CFTR gene. This gene controls the movement of salt and water in and out of the body’s cells.

When the CFTR gene does not work properly, it causes the body to produce thick, sticky mucus. This mucus builds up in the lungs, digestive system, and other organs, leading to the symptoms and complications associated with CF.

CF is passed down through families

To be born with cystic fibrosis, a child must inherit two faulty copies of the CFTR gene — one from each parent.

• A person who has only one faulty copy is known as a carrier
• Carriers do not have CF themselves, but they can pass the gene on 
• If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will be born with CF

How common are CF carriers?

Around 1 in 25 Australians carry a faulty CF gene. Most do not know they are carriers until they have a child with CF or undergo genetic testing.

Carrier screening is available in Australia and you can read more about it here.

Different mutations, different outcomes

There are more than 2,000 known mutations in the CFTR gene, The most common mutation worldwide is called F508delta or F508del for short, which is also the most common in Australia.

The type and combination of mutations a person has can influence:

• How severe their symptoms are
• What treatment options are available, particularly CFTR modulators

This is why genetic testing is an important part of diagnosis and personalised treatment planning.

Classes of CFTR Mutations

While there are thousands of CFTR mutations, they can be grouped into five main classes based on how they affect the CFTR protein. Each class disrupts the protein in a different way – from stopping it being made at all, to changing its shape, or limiting how well it works at the cell surface.

Understanding these classes helps explain why CF can look different from person to person and why some treatments work for certain mutations but not for others.

• Class I – Protein Production Mutations – protein isn’t made correctly
  These mutations occur when the components of the CFTR protein called amino acids arrange in a way to does not correctly make the CFTR protein.  These include nonsense and splice mutations. People with two Class 1 mutations are less likely to respond to currently available modulator therapy in Australia.
• Class II – Protein processing mutations -protein made but not transported to the cell surface
  The CFTR protein is created, but it’s the wrong shape. Because of this, it cannot reach the surface of the cell where it is needed to transport chloride.  The most common CF mutation (F508del) is in this group.  Currently available modulator therapy in Australia can assist with this mutation class because it can help the protein fold into the correct shape and be able to move some chloride.
• Class III –Gating mutations – Protein reaches the surface but won’t open
  Here, the CFTR protein is made and is the right shape and does get to the cell surface, but it doesn’t function properly. The protein needs to function as a gate to allow chloride to move through, so it needs to open and close at the right time. In these kinds of mutations, the ability of chloride to move correctly in and out of cells is limited.

The first three classes are thought to lead to the most severe disease.

• Class IV –Conduction mutations – Protein reaches the surface, and gate can open but the gate is the wrong shape.
  The CFTR protein reaches the cell surface and is the right shape, and the gate can open, but the shape of the gate or channel isn’t correct. The channel works, but only weakly. 
• Class V – Insufficient protein mutations- Not enough protein is made and there is some or residual function of the gate
  In this case, the CFTR protein is normal, but the gene doesn’t make enough of it. So, there’s some function, but not as much as needed.

Who can be affected?

CF can affect people of any background or ethnicity. While it is more common in people of northern European descent, this is most likely due to poor access to screening and testing in other countries. Because of this, awareness and access to testing are important across all communities.