What is the role of CFTR mutations in the pathogenesis of cystic fibrosis (CF)?

Updated: Oct 22, 2019
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Six classes of defects resulting from CFTR mutations have been described and are as follows [5] :

  • Complete absence of CFTR protein synthesis

  • Defective protein maturation and early degradation (caused by the most common mutation, ΔF508)

  • Disordered regulation (diminished ATP binding and hydrolysis)

  • Defective chloride conductance or channel gating

  • Diminished transcription due to promoter or splicing abnormality

  • Accelerated channel turnover from the cell surface

CFTR mutations have poor penetrance. This means that the genotype does not predict the pattern or severity of disease.

Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells. The resultant reduced height of epithelial lining fluid and decreased hydration of mucus results in mucus that is stickier to bacteria, which promotes infection and inflammation. Secretions in the respiratory tract, pancreas, GI tract, sweat glands, and other exocrine tissues have increased viscosity, which makes them difficult to clear.

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