V520f

[amykay1965]

My 19 year old daughter has the Delta F508 mutation and V520F. We attended CF family education day today and although they gave us the website to research mutations, I'm still confused. Which category does V520F fall in? Is it a mutation that the new medicines might help? I know with Delta F508 you need a drug to make the CFTR and then Kalydeco to release it but what about V520f?

 

[GenH]

I did a google search looking for information and articles about V520F, but there does not seem to be much information. Some people have posted in the UK that they believe it is a class 3 gating mutation. I have not found any evidence to support this, but if it is a gating mutation Kalydeco may help. Maybe your doctor can find out more information?
http://www.cftrust.org.uk/forum/viewtopic.php?p=91489&sid=a19237c7ec725a8eabac5fa88ba006a5

 

[brandonalbert]

I wish I knew the answer to this too. There does not seem to be much info out there on v520f. If you hear or read any news please let us know! I will do the same.

 

[kyeev]

Here are a couple of publications that state V520F is a class III mutation:

http://www.ncbi.nlm.nih.gov/pubmed/11180668
http://www.ncbi.nlm.nih.gov/pubmed/19403164

Seeing as there does not appear to be any definitive research published on V520F, I'm guessing it has been assigned to class III by ruling out the other classes.
It can't be class I as they are all splicing defects with no protein production or stop mutations that end with an X.
Since V520F causes classical CF symptoms when inherited with a known severe mutation, say DF508, this rules it out of class IV and V (which are mild).
So it can only be class II or III.
Its a missense mutation, which means it codes a Valine instead of a phenylalanine at position 520.
This amino acid change may not to be as problematic as say a DF508 amino acid deletion with regards trafficking to the cell membrane so probably rules it out of class II, which results in a best guess of class III.
CFTR2 in vitro data suggests it does not mature normally and has a low chloride conductance, but are awaiting peer review on their research.

EDIT: New information shows kalydeco/ivacaftor monotherapy has no effect on V520F. Which sucks...