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CFTR Mutations and Activity: The clinical impact of reduced CFTR activity

The potential clinical impact of an individual CFTR mutation may be related to the amount of total CFTR ion transport activity. Total CFTR activity is associated with the extent of CF manifestations and phenotypic variability.1-5

Spectrum of phenotypes associated with total CFTR activity1,3-5

Reduction in total CFTR
activity causes various phenotypes, including CFTR-related disorders and cystic fibrosis

Total CFTR activity is a function of how each CFTR mutation affects6:

  • CFTR quantity: the number of CFTR channels at the cell surface
  • CFTR function: the functional ability of each channel to open and transport ions

Individual CFTR mutations can decrease the quantity or function (and sometimes both) of CFTR proteins at the cell surface. These defects in CFTR protein cause a reduction in total CFTR activity.1,6,7

CFTR quantity and function defects reduce total CFTR activity1,6

CFTR quantity and function defects determine the amount of total CFTR activity

To what extent do different CFTR mutations affect total CFTR activity? Learn more.

    References:
  1. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration. 2000;67(2):117‐133.
  2. Castellani C, Cuppens H, Macek M, et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008;7(3):179-196.
  3. Rowe SM, Accurso F, Clancy JP. Detection of cystic fibrosis transmembrane conductance regulator activity in early-phase clinical trials. Proc Am Thorac Soc. 2007;4(4):387-398.
  4. Davis PB, Drumm M, Konstan MW. Cystic fibrosis. Am J Respir Crit Care Med. 1996;154(5):1229-1256.
  5. Bombieri C, Claustres M, De Boeck K, et al. Recommendations for the classification of diseases as CFTR-related disorders. J Cyst Fibros. 2011;10(Suppl 2). doi:10.1016/S1569-1993(11)60014-3.
  6. Sheppard DN, Rich DP, Ostedgaard LS, Gregory RJ, Smith AE, Welsh MJ. Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties. Nature. 1993;362(6416):160-164.
  7. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993;73(7):1251-1254.