There are more than 1000 different mutations in the CFTR gene that can cause CF. Most mutations either substitute one DNA base - the building material of DNA - for another or delete a small number of DNA bases entirely. The most common mutation in about 70 percent of CF patients is called delta F508 or ?F508. This change, or delta, is caused by the deletion of three base pairs from the CFTR gene DNA. This leads to the loss of an amino acid called phenylalanine in the CFTR protein. Each person receives one copy of the CFTR gene from each parent. To have CF, both copies of the genes must be mutated in some way, but the mutations do not have to be the same. If a person received one normal gene and one mutated gene, these people will not have any CF symptoms, but will be considered carriers. One in 31 Americans has one copy of a defective CFTR gene.
There are many ways that different mutations in the CF gene can change CFTR function. Patients who have some normal CFTR reaching the cell surface tend to have milder symptoms. Five functional classes of CF mutations are described (Class of mutation - CFTR production and function) Class 1 mutations
CFTR production is stopped early and protein production becomes defective. Class 1 patients have few or no functioning CFTR chloride channels. Class 2 mutations
The CFTR has difficulty reaching its final placement on the apical surface cell membrane where it can function. Class 3 mutations
Even though the CFTR reaches its correct final placement on the apical surface of the cell membrane, there are problems with the CFTR itself. Class 4 mutations
CFTR reaches the apical surface but conduction of sodium and chloride through the channel is defective. Class 5 mutations
Associated with reduced synthesis of functional CFTR. A small amount of function CFTR may reach the surface
| 
