Forgot your password?
Please enter your username or email address. Instructions for resetting the password will be immediately emailed to you.
Please note: While some information will still be current in a year, other information may already be out of date in three months time. If you are in any doubt, please feel free to ask.
Mild mutations
- Question
- Hello,
Are there mutations that make the disease milder than others?
Thank you.
- Answer
- Hello,
CF patients carry two mutations in the CFTR gene. There are over 1800 mutations of this gene. A single mutation is really common, the delta F508 mutation (or F508del), found in about 70% of patients. The CFTR gene encodes the synthesis of a CFTR protein normally located at the apical membrane of our cells. By allowing the secretion of chloride ions outside the cell and inhibiting the absorption of sodium ions into the cell, the CFTR protein allows normal hydration of the extracellular medium. In patients with cystic fibrosis, the dysfunction of this protein leads to a thickening of extracellular fluids.
CFTR gene mutations have been grouped into classes according to their variable effects on the CFTR protein and its functions:
- Class 1: mutations altering the production of the protein
- Class 2: mutations altering the cellular maturation of the protein; the protein is either absent or in very small quantity to the cell membrane. The F508del mutation is part of this class.
- Class 3: mutations disturbing the regulation of the CFTR protein that is located in the membrane, but the chloride channel is not functioning
- Class 4: mutations altering the conduction of the chloride channel, with a decrease in the flow of chloride ions secreted
- Class 5: mutations resulting in reduced synthesis of the CFTR protein
- Class 6: mutations altering the stability of the CFTR protein.
Patients with at least one mutation in classes 4, 5 and 6 have generally a less severe disease than patients with 2 mutations in classes 1, 2 and 3. In particular, they are less likely to have pancreatic insufficiency.
However, these classes of mutations are used for research purposes and may be useful at population level to determine associations, but do not predict the course of the disease in individual patients. Indeed, other genetic factors (modifier genes) and environmental factors are involved in determining the characteristics and severity of the disease. This explains why brothers and sisters with cystic fibrosis, thus having the same CFTR mutations, can have symptoms and evolution of their cystic fibrosis that can be quite different.
Best regards.
Dr Dominique Hubert
- 19.07.2011
