CF mutation

Question

Hello,
can you explain what does it mean that the F508del mutation of the CFTR gene has been found in my 5.5 year-old daughter, and what are the consequences for her respiratory as well digestive health?
Thank you

Answer

Hello,
The genetic test shows that your girl has an homozygous F508del mutation genotype (as half of the patients with cystic fibrosis): homozygous means she carries the mutation in duplicate, one inherited from her father and one from her mother.
We know to date more than 1,900 mutations in the CFTR gene. Apart from the F508del mutation, most of these mutations are rare or very rare or exceptional. The symptoms associated with these mutations vary between mutations leading to a diagnosis of a classical form of cystic fibrosis, an attenuated form or an atypical form of uncertain diagnosis.
The presence, in one person, of two mutations known to cause cystic fibrosis, suffices the diagnosis of the disease. This is the case in your daughter.
Databases that combine information from several thousand patients support a finding that F508del patients, except rare exceptions, have a positive sweat test, pancreatic insufficiency and respiratory symptoms. In practice, however, the knowledge of mutations (genotype) is not enough, by itself, for predicting evolution of the disease in a given individual because it depends on many other factors, environmental factors or other genetic factors such as modifier genes.
This is the justification for a regular follow up of patients in a specialized CF Center by a multidisciplinary team.
Hope that answers your question.
Sincerely.
Gilles RAULT, MD
Roscoff CF Centre

10.09.2014