Doctors have identified five categories of cystic fibrosis transmembrane conductance regulator (CFTR) genes. A person who inherits one copy of a mutated gene from each biological parent develops cystic fibrosis.
CFTR mutations are recessive, which means a person must inherit two copies of the gene to develop cystic fibrosis. People who inherit one mutation from a biological parent become carriers who can pass the gene and the condition onto their children. Those who inherit two mutations develop cystic fibrosis.
The type of mutation someone carries can influence the severity of the condition and the treatment options that may be available.
Read on to learn about types of cystic fibrosis gene mutations.
Researchers divide cystic fibrosis mutations into
Class 1: Protein production mutations
Protein production mutations occur when the amino acids that build proteins arrange in a way that does not correctly code for the CFTR protein. Typically, there is a code to stop the production of the protein at the appropriate time. A nonsense protein mutation causes production to stop too early.
Another protein production mutation, a splice mutation, contains irrelevant code that makes it impossible for the cell to read the genetic code for the protein correctly.
Class 2: Protein processing mutations
Typically, the CFTR protein forms a specific three-dimensional shape that tells the cell how to use it correctly. Protein processing mutations cause incorrect amino acids to be added or deleted. This changes the shape of the CFTR protein.
This mutation prevents CTFR from moving to the right location in the cell.
Class 3: Gating mutations
The CFTR protein functions as a gate through which chloride can move through. The gate otherwise stays closed.
Gating mutations prevent the gate from opening fully, limiting or eliminating the ability of chloride to move through to the cell.
Class 4: Conduction mutations
Some mutations causing changes in one or more amino acids forming the CFTR protein allow it to make the right shape. However, they hinder the protein’s function. This may slow the movement of protein through the protein channel and into the cell. This is a conduction mutation.
Class 5: Insufficient protein mutations
Insufficient protein mutations mean there is not enough CFTR protein in each cell. This can occur because the body does not produce enough CFTR, because only some of the CFTR works, or because the protein at the surface of the cell breaks down too quickly.
This reduces the function of the chloride channel.
One of the most common complications of this mutation is exocrine pancreatic insufficiency. It is a condition where the small intestine
Cystic fibrosis mutations are genetic changes that people pass from one generation to the next.
A parent passes the damaged gene to their biological child. If both parents pass on a damaged gene, the child will develop cystic fibrosis.
An expanded blood test can determine the specific genetic mutation a person has.
The type of cystic fibrosis mutation a person has is important in determining the symptoms they have and the severity of symptoms.
Doctors categorize classes 1, 2, and 3 as classic cystic fibrosis, which typically causes more severe symptoms. Classes 4 and 5 are typically a milder form of the disease.
Treatment for cystic fibrosis
However, several new treatments target specific genetic mutations.
For example, Trikafta helps CFTR proteins fold in a more appropriate shape when a person carries an F508 delta protein processing mutation. Trikafta comprises a combination of lumacaftor, tezacaftor, and ivacaftor.
Ivacaftor can reduce the symptoms of gating mutations by forcing the CFTR channel open, enabling chloride to travel through.
These drugs do not cure cystic fibrosis but can improve the functioning of the CFTR protein, thereby improving symptoms. That said, a person may still need other treatments.
The genetic mutation a person inherits directly influences the severity of cystic fibrosis.
While five types of mutations exist, there are thousands of individual mutations, each with its own specific effects.
Identifying the mutation may support better and more effective treatments since several medications target specific mutations.