Overview
Clinical Meaning
Cystic fibrosis (CF) is caused by mutations in the CFTR gene encoding the CF transmembrane conductance regulator — a chloride and bicarbonate channel on epithelial cell surfaces.
Cystic fibrosis (CF) is caused by mutations in the CFTR gene encoding the CF transmembrane conductance regulator — a chloride and bicarbonate channel on epithelial cell surfaces. The most common mutation, F508del (70% of alleles), causes protein misfolding, ER retention, and proteasomal degradation. Defective CFTR reduces chloride and water secretion into airway lumen while increasing sodium reabsorption via ENaC (epithelial sodium channel), producing thick, dehydrated mucus. In the lungs, this impairs mucociliary clearance, creating a favorable environment for chronic bacterial colonization (Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia). In the pancreas, duct obstruction causes pancreatic insufficiency (85-90%). CFTR modulators (elexacaftor/tezacaftor/ivacaftor — Trikafta) have transformed CF from a pediatric disease to an adult chronic disease, with median predicted survival now exceeding 50 years.