Cystic Fibrosis

Question 1

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 1 mutation?

Answer 1

No CFTR protein is produced at all. This is the most severe type.

Cystic Fibrosis Transmembrane Conductance Regulator

Question 2

What are the meaningful values for the sweat chloride test?

This is hte gold standard for diagnosis of CF

Answer 2

Question 3

What is CFTR?

Answer 3

Cystic Fibrosis Transmembrane Conductance Regulator

Question 4

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 2 mutation?

Answer 4

CFTR doesn’t reach the cell surface. It can’t make it to the membrane. It’s stuck in the cell and can’t leave. The actual transmembrance regulator can’t get to the membrane, has nothign to do with chloride.
F508del mutation

Cystic Fibrosis Transmembrane Conductance Regulator

Question 5

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 3 mutation?

Answer 5

Non-functional protein within the cell membrane. It is sitting within the cell membrane but can’t function. Inactive CFTR.
G551D missense mutation

Cystic Fibrosis Transmembrane Conductance Regulator

Question 6

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 4 Mutation?

Answer 6

Defective chloride transport through the channel.This means less chloride is being transfered out.This is a physical problem with the channel but it kind of functions.
Defective CFTR

Cystic Fibrosis Transmembrane Conductance Regulator

Question 7

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 5 Mutation?

Answer 7

Decreased amount of protein at the cell surface. Basically, not enough of the protein.
Less CFTR

Cystic Fibrosis Transmembrane Conductance Regulator

Question 8

Cystic fibrosis can be caused by one of 6 classes of mutations:

What is a Class 6 Mutation?

Answer 8

Unstable protein leading to decreased amount at cell surface. It gets degraded quicker (like a shorter half-life). They work, they just don’t last for very long.
Accelerated turnover.
Unstable/decreased amount of surface CFTR

Cystic Fibrosis Transmembrane Conductance Regulator

Question 9

Answer 9

Review the classes

Question 10

Whcih classes are function and which are quantity related to CFTR?

Answer 10

Class I & II & V & VI: quantity
Class III & IV: function