Cystic Fibrosis Flashcards
What classes of CF mutations are considered classic?
I, II, and III
What classes of CF mutations are considered mild?
IV, V, and V
What do Class I CF mutations impact?
Faulry mRNA not translated
results in reduced or absent synthesis
15% of all CF patients (higher in Israeli patient populations)
What do Class II CF mutations impact?
misfolding and degradation of CFTR protein
results in block in protein processing
80% of CF patients
What do Class III CF mutations impact?
defective regulation of CFTR
results in blockage of CFTR chloride channel
4% of all patients
What do Class IV CF mutations impact?
chloride channel conduction defects
What do Class V CF mutations impact?
reduced amounts of mRNA
What do Class VI CF mutations impact?
CFTR abnormally regulates OTHER channels
Name and describe the kinds of CFTR modulators.
potentiators (hold open chloride channels)
correctors/modifiers (help form proper 3D shape for trafficing)
amplifiers (increase amount of CFTR protein cells make)
What mutations are commonly associated with Class I CF?
nonsense G542X
frameshift 394delTT
splice junction 1717-1Gā>A
What mutations are commonly associated with Class II CF?
missense N1303K
AA deletion deltaF508
What mutations are commonly associated with Class III?
G551D
Name the two common modifier mutations in CF.
5T and R117H
What kind of modulator is most appropriate for Class III CF patients?
potentiators
example: Ivacaftor (good for G551D mutations)
What kind of modulator is most appropriate for Class II CF patients?
modifiers
examples: Orkambi (good for 2x delF508)
Symdeko (2x delF508 or 1x of 26 other mutations)
Trikaftor (1x delF508)
