CF Flashcards
0
Q
Major clinical signs? Percent of CFTR function for each?
A
10%cbavd
4% airway prob and sweat
<1% pancreatic insufficiency
1
Q
Frequency of CF carriers in caucasians?
A
1/30
2
Q
Where exactly is the CF gene?
A
7q
3
Q
Class I: what is affected? Mutation? Result? Frequency?
A
- Transcription
- missense, frame shift, splice
- no protein is produced
- 5-10%
4
Q
Class II: what is affected? Mutation? Result? Frequency?
A
- Post-transcription
- missense
- degraded and does not reach membrane (F508)
- 85%
5
Q
Class III: what is affected? Mutation? Result? Frequency?
A
- Activation
- Missense
- ATP/cAMP regulation disfunction (G551D)
- 2-4%
6
Q
Class IV: what is affected? Mutation? Result? Frequency?
A
- Decreased conductance
- Missense
- Less Cl- transport; R117H
- 2%
7
Q
Class V: what is affected? Mutation? Result? Frequency?
A
- Processing defect
- Missense
- Less protein at PM
- 1%
8
Q
Severity of phenotype in R117H?
A
Poly-T tract (5T, 7T, 9T): shorter tail is more severe TG tract (11TG, 12TG, 13TG): longer tail is more severe
9
Q
Structure of CFTR?
A
ATP binding cassette (ABC) - 2 membrane spanning domains - 2 ATP binding cassettes (nucleotide binding domains NBD) - 1 regulatory domain (made in ER, sugar chain added in golgi)
10
Q
CFTR channel opening process?
A
cAMP PKA phosphoryates regulatory domain
ATP binding to NBD1 –> transient open
ATP binding to NBD2 –> stabilize open
11
Q
What does bicarb have to do with pancreatic insufficienccy?
A
CF decreased bicarb production from from pancreatic acinar cells –> lowered pH –> blocks duct
12
Q
CF Newborn screen process
A
- IRT (immunoreactive trypsinogen) - elevated
- 4% –> 42 mutation gene testing
- confirm with blood test and sweat Cl- test (>60 mmol/L; nrml 40)
13
Q
Only cure for CF?
A
Kalydeco (lvacaftor)
- G551D (Class III)
- binds and opens gate
14
Q
What is a normal sweat Cl level? CF?
A
40mmol/L
>60
15
Q
What is a normal sweat Cl level? CF?
A
40mmol/L
>60
