Cystic fibrosis is an autosomal recessive genetic disorder that affects multiple organs and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of chromosome 7. It is a major cause of exocrine pancreatic insufficiency in infancy and severe chronic lung disease in childhood. The condition can also lead to nasal polyps, chronic sinusitis, gallstones, pancreatitis, rectal prolapse, non-autoimmune insulin-dependent hyperglycemia, growth failure, liver cirrhosis, and impaired liver function.
What Causes Cystic Fibrosis?
The CFTR gene contains 27 exons and encodes the CFTR protein, which is composed of 1,480 amino acids. This protein is located in the epithelial cell membrane and functions as a chloride ion channel, primarily distributed in the respiratory tract, gastrointestinal tract including the pancreas and biliary system, sweat glands, and the urogenital system such as the epididymis and fallopian tubes.
Abnormalities in the CFTR protein lead to impaired chloride ion secretion from the cells, resulting in increased reabsorption of chloride and water through epithelial cells. This increases the viscosity of airway mucus, impairing sputum clearance, which in turn leads to recurrent infections, bronchiectasis, and progressive pulmonary fibrosis.
The most common mutation is known as F508del, caused by the deletion of a phenylalanine residue at position 508.