CFTR Overview and Mutation Classes

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.

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.