CFTR Overview and Mutation Classes

Questions and Answers

What is the normal CFTR description?

CFTR protein is created, moves to cell surface and allows transfer of chloride and water.

What is the Class I mutation description?

CFTR protein is created in insufficient quantities

CFTR protein is created but misfolds

CFTR protein is functional but the channel gate does not open

No functional CFTR is created (correct)

What kinds of mutations are Class I mutations?

Nonsense, splicing, deletion mutations.

What is the Class II mutation description?

CFTR protein is created but misfolds Signup and view all the answers

Which percentage of people carry Class II mutations?

88% Signup and view all the answers

What is the common mutation for Class III?

G551D Signup and view all the answers

What happens in Class IV mutations?

CFTR protein is created and moves to the cell surface, but the function of the channel is faulty. Signup and view all the answers

What is the description for Class V mutations?

Normal CFTR protein created and moves to the cell surface, but in insufficient quantities. Signup and view all the answers

What potential therapy is suggested for Class I mutations?

Read-through compounds that may allow the production of full-length CFTR for nonsense mutations. Signup and view all the answers

Which drugs help in the treatment of Class II mutations?

Correctors such as Lumacaftor or Tezacaftor. Signup and view all the answers

What do potentiators do for classes III, IV, and V?

They help open the CFTR channel and increase the function of normal CFTR. Signup and view all the answers

What does the CFTR protein control?

The salt and water balance in the lungs and other tissues. Signup and view all the answers

How many copies of the CFTR gene does each human have?

2 Signup and view all the answers

How many mutated copies are needed to have CF?

2 Signup and view all the answers

What do gene editing techniques aim to do?

Repair the underlying genetic defect in the CF gene DNA. Signup and view all the answers

What do gene replacement strategies aim to do?

Provide a correct copy of the CFTR gene. Signup and view all the answers

What is the goal of RNA therapies?

Either fix the incorrect instructions in defective RNA or provide normal RNA directly to the cell. Signup and view all the answers

What do read-through compounds aim to do?

Allow full-length CFTR protein to be made even when the RNA contains a mutation stopping production. Signup and view all the answers

What do correctors do in the context of CFTR mutations?

Drugs that help the defective CFTR protein fold properly so that it can move to the cell surface. Signup and view all the answers

What do potentiators do?

Help open the CFTR channel at the cell surface and increase chloride transport. Signup and view all the answers

Study Notes

CFTR Overview

CFTR protein facilitates chloride and water transport, crucial for maintaining salt and water balance in lungs and other tissues.
Each human has two copies of the CFTR gene; both must be mutated for cystic fibrosis (CF) to develop.

CFTR Mutation Classes

Class I: No functional CFTR produced; accounts for 22% of mutations. Common mutation: G542X. Known as "production mutations."
Class II: CFTR protein is created but misfolded, preventing it from reaching the cell surface. Occurs in 88% of cases. Common mutation: F508del. Referred to as "processing mutations."
Class III: Functional CFTR protein reaches the surface, but the channel gate fails to open correctly. Represents 6% of mutations. Common mutation: G551D. Labeled as "gating mutations."
Class IV: CFTR protein is present but its channel function is impaired. Also accounts for 6% of mutations. Known as "conduction mutations."
Class V: Normal CFTR is produced but in insufficient quantities.

Potential Therapies

Class I Therapies: Read-through compounds can help produce full-length CFTR, bypassing nonsense mutations.
Class II Therapies: Correctors like lumacaftor or tezacaftor aid in proper folding of CFTR, allowing it to reach the cell surface effectively.
Classes III, IV, and V Therapies: Potentiators, such as ivacaftor, facilitate the opening of CFTR channels and improve function of both defective and normal CFTR.

Gene Editing and RNA Therapies

Gene Editing: Aims to repair the genetic defect in CF gene DNA directly.
Gene Replacement: Seeks to supply a correct version of the CFTR gene.
RNA Therapies: Focus on correcting defective RNA instructions or providing normal RNA to cells.
Read-Through Compounds: Enable the synthesis of full-length CFTR even with stop mutations (Class I).
Correctors: Support proper folding of defective CFTR for effective surface transport (Class II).
Potentiators: Enhance channel opening at the surface, boosting chloride transport (Classes III, IV, and V).

Important Considerations

Understanding different mutation classes assists in identifying targeted treatment approaches for cystic fibrosis.
The variety of therapeutic strategies reflects the complexity of CFTR mutations and the variability in patient presentations.

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Description

This quiz covers the CFTR protein's role in chloride and water transport, essential for maintaining balance in various tissues. Additionally, it explores the different classes of CFTR mutations and their implications for cystic fibrosis development. Test your knowledge on the genetics of CFTR and its mutations.