Cystic Fibrosis

Cystic fibrosis (CF) is an inherited disease in which thick, sticky mucus builds up in the lungs, pancreas and other organs. It is caused by mutations in the CFTR gene on chromosome 7, and it is the most common life-shortening inherited disease among people of European ancestry.

CFTR encodes a channel in the cell membrane that lets chloride ions out of cells, and water follows. Without a working channel, secretions become dry and thick. The most common mutation, ΔF508, is a deletion of three bases that removes one phenylalanine, causing the protein to misfold and be destroyed before it reaches the surface. CF is autosomal recessive, so a child needs two defective alleles, and about 1 in 25 people of European ancestry is a carrier, a number that follows the Hardy-Weinberg principle.

Mucus blocks airways and traps bacteria such as Pseudomonas aeruginosa, causing repeated lung infections that become hard to treat because of antimicrobial resistance. The pancreas ducts are blocked, so digestion of fat is poor, and the sweat is unusually salty, which is the basis of the standard diagnostic sweat test. Median survival has risen from childhood to about 50 years or more in places with modern care.

Airway clearance, antibiotics and enzyme supplements remained the core of care for decades. Since 2012 CFTR modulator drugs, starting with ivacaftor and followed by combinations such as elexacaftor, tezacaftor and ivacaftor, have corrected the defective protein in most patients and improved lung function. The gene was identified in 1989, and attempts at gene therapy continue. The disease is a textbook case of a genetic mutation in an ion channel, related to active transport.

• Hardy-Weinberg Principle — used to calculate carrier frequency
• Gene Therapy — a treatment approach under study
• Genetic Mutation — the cause of the disease