More than 1000 different mutations in the CFTR gene can cause CF. Most of these mutations either substitute one DNA base - the building material of DNA - for another, or delete a small number of DNA bases altogether. The most common mutation present in approximately 70 percent of CF patients is called delta F508 or ?F508. This change, or delta, is caused by the deletion of three base pairs of the CFTR gene that lead 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, a mutation must be present on both copies of the CFTR genes, but the mutations do not have to be the same. If a person received one normal gene and one mutated gene, he or she will not have any CF symptoms, but will be a carrier. One in 31 Americans has one copy of a defective CFTR gene. There are several mechanisms by which mutations in the CF gene produce changes in CFTR function. Patients who have some normal CFTR reaching the cell surface tend to have milder symptoms. Five functional classes of CF mutations have been described Class 1 mutations
Defective protein production with premature termination of CFTR production. Class 1 mutations produce few or no functioning CFTR chloride channels. Class 2 mutations
Defective trafficking of CFTR so that it does not reach the apical surface membrane where it can function. Class 3 mutations
Defective regulation of CFTR even though it is able to reach the apical cell surface. Class 4 mutations
CFTR reaches the apical surface but chloride transport through the channel is defective. Class 5 mutations
Reduced synthesis of functional CFTR. A small amount of functional CFTR may reach the surface.
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