Although we know of over 2,000 different mutations in the CFTR* gene, only 242 of these cause cystic fibrosis (CF) and most are extremely rare.1 If both of the CFTR genes you inherit from your parents have a mutation that does cause CF, your body produces defective CFTR protein channels.2
Depending on the type of each mutation, this may lead to decreased numbers of CFTR proteins at the cell surface, CFTR proteins that do not work correctly, or both.
When CFTR proteins do not work correctly the channels do not stay open long enough, do not open as often as they should or are too narrow.3
When there are too few CFTR proteins at the cell surface this can be due to gene mutations that cause the CFTR building instructions to be made incorrectly, or read incorrectly, by the parts of the cell that build the CFTR protein. Other mutations can cause faulty proteins to be produced that are destroyed by the cell before reaching the cell surface, or proteins which are unstable and are removed too quickly from the cell surface.3
Too few CFTR proteins:
CFTR proteins not working correctly:
Having too few CFTR proteins at the cell surface, or CFTR proteins that do not work correctly means water and molecules such as chloride ions cannot move freely in and out of cells, which may eventually lead to thick, sticky mucus in the lungs and other parts of the body. This may disrupt organ functioning and cause symptoms of CF.3
Different mutations have different effects on CFTR protein channel functioning.4
*CFTR = Cystic fibrosis transmembrane conductance regulator
1. US CF Foundation, Johns Hopkins University, The Hospital for Sick Children. The Clinical and Functional Translation of CFTR (CFTR2). Available from: http://www.cftr2.org/files/CFTR2_13August2015.pdf. Accessed June 2016.
2. Orenstein DM. Cystic Fibrosis: A Guide for Patient and Family. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.
3. Derichs N. Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis. European Respiratory Review 2013; 22(127): 58 ̶ 65.
4. Welsh MJ, Ramsey BW, Accurso F, Cutting GR. Cystic fibrosis: membrane transport disorders. In: Valle D, Beaudet A, Vogelstein B, et al. eds. The Online Metabolic & Molecular Bases of Inherited Disease. The McGraw-Hill Companies Inc; 2004: part 21, chap 201. www.ommbid.com.