F508del and G542X

Question

My 4 months old son has been diagnosed with CF. He has the above mentioned mutations. How severe is this combination? I'm extremely worried about what might happen to him one day. Thank you.

Answer

Dear Questioner
Thank you for posting your question on our site.

There are many mutations that can cause cystic fibrosis. Some can cause mild dysfunction of the CFTR protein and therefore cause milder disease. And there are others that cause greater dysfunction of CFTR protein and generally more severe disease. It is however difficult to predict with certainty, the clinical presentation and future course of a patient’s condition based only on their genetic information. People with the same two copies of the mutated CFTR gene may experience very different symptoms. There are many factors that can influence cystic fibrosis disease. These can include factors from the patient’s environment (for example, exposure to tobacco smoke and nutrition). A very important environmental factor is the person’s therapy. The improvements in survival over the past 5 decades shows the benefits of intense treatment which includes pancreatic enzymes, intensive nutritional support, antibiotics for pulmonary infections, aggressive physiotherapy and multidisciplinary care (Castellani et al 2008).

There is a large database which gathers information on the clinical outcomes of patients with different mutations (www.cftr2.org/). It should be noted that this can only give us trends for groups of patients, and cannot tell us exactly what is likely to happen to one particular individual. This database lists G542X and describes it is a severe mutation (Class 1, nonsense mutation). This means that the CFTR protein building stops too early and the protein made does not function. This mutation is generally associated with lung disease and pancreatic insufficiency. In the CFTR2 database we see that F508del too is associated with lung disease and pancreatic insufficiency. The severity of lung disease described in this group of people has a wide range; some are relatively mild and some are more severe.

We would advise you to talk to a cystic fibrosis specialist team about any concerns and about what your son’s therapy should involve. They would be able to give more specific advice after a face-to-face consultation with your son.

Best wishes,
Lisa Kent and Stuart Elborn
(Belfast)


Castellani et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. Journal of Cystic Fibrosis 2008;7:179-196

15.10.2013

The answer is edited by: PhD Lisa Kent