genetics

Question

(to dr Sobczyńska)
Are the mutations F508 del and R334W, if present together, severe form of CF and what is the prognosis? Should any special treatment of the CF patient be introduced?

Answer

Dear Questioner,
Compound-heterozygosity (meaning that there are two different mutations on each of the two genes) for F508del and R334W represents a genotype which leads to cystic fibrosis. The CF-phenotype ("severety of disease") is not predictable. R334W is a class 4 mutation, which (in compound-heterozygosity with other typical CF mutations) has been seen in CF patients with pancreatic sufficiency (PS), as well as in patients with pancreatic insufficiency (PI).
Therefore, in the recent recommendations by Castellani et al. (Journal Cystic Fibrosis 2008, 7:179-196), R334W has been classified as a one of the very few examples of CF mutations which are present in both PS and PI patients. With respect to lung function, there is no predictable outcome.
To date, there is no mutation/genotype specific treatment of CF. However, this may change in the future, because for some mutations or mutation classes, specific treatment is under development or even tested in clinical trials. This is also the case for F508del (a class 2 mutation), where specific pharmacologic
approches are currently tested. Of course, today it is not known whether these specific treatment trials will be successful enough to enter daily practise.
Summary: F508del/R334W is a well known CFTR genotype, which is leading to CF with a wide phenotipic range. Today, there is no special treatment for patients with this genotype.
Best regards, Natalia Kobelska-Dubiel, MD, PhD together with Prof. Dr. M. Stuhrmann-Spangenberg

03.02.2009