cystic fibrosis

cystic fibrosis

Ireland has the highest incidence of CF in Europe. It is characterised by chronic lung infections and lung damage. >1000 mutations but 70% are associated with a defective chloride ion transporter.

CF transmembrane conductance regulator (CFTR)

ABC transporter. Normally allows Cl- ions to flow out of the cell following their concentration gradient. Cl- flux is accompanied by Na+ and water.

Binding of 2 ATP molecules appears to open the channel. Hydrolysis of one ATP closes the channel. Maintains proper fluidity of the mucus in the respiratory tract, pancreas, sweat glands.

delta F508 cystic fibrosis

This is a specific mutation within the gene for a protein called the CFTR. The mutation is a deletion of a single codon for the amino acid phenylalanine (F). Results in an abnormal CFTR protein that cannot fold properly.

Does not escape the endoplasmic reticulum for further processing. Having 2 copies of this mutation is by far the most common cause of cystic fibrosis, responsible for nearly 2/3 of cases worldwide.

mutations of CFTR gene 

Mutations of the CFTR gene affecting chloride ion channel function leading to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis. Complications include thicken mucus in the lungs, with frequent respiratory infections and pancreatic insufficiency giving rise to malnutrition and diabetes.

The conditions lead to chronic disability and reduced life expectancy.

treatments for CF

• Antibiotics to prevent and treat chest infections

• Mucus thinners

• Medicines to widen the airways and reduce inflammation

• Physiotherapy to help clear mucus from the lungs

• Transplant

• Combination treatment with CFTR modulators: elexacaftor, ivacaftor and tezacaftor