Cystic fibrosis

Cystic Fibrosis

Cystic Fibrosis is an autosomal recessive disease located on chromosome 7. Cystic Fibrosis is caused by a mutation to the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) channel. The most common mutation is ΔF508, accounting for 70% of mutations in the Caucasian UK population, in which the triplet code (codon) for the amino acid phenylalanine is deleted, disrupting Cl^- transport. This mutation belongs to the Class II group of mutations causing Cystic Fibrosis.

CFTR is composed of 3 types of domains. There are 12 Transmembrane spanning domains, 2 Nucleotide Binding Domains (NBD’s) and an R domain (regulatory domain). The NBD’s are involved in the binding and hydrolysis of ATP.

CFTR is part of the ABC (ATP Binding Cassette) superfamily of transporters.

Cystic Fibrosis Classes

Class I: Premature Stop Codons (e.g. W1282X)

Class II: Abnormal Processing (e.g. ΔF508)
This involves the deletion of the amino acid, Phenylalanine at NBD1 (Nucleotide Binding Domain 1) of the CFTR (Cystic Fibrosis transmembrane conductance receptor). This mutation takes effect on the processing of the protein after leaving the Endoplasmic Reticulum. It adversely comprimises the trafficking/passage of the protein across the cytosol ultimately resulting in the the protein being degraded by the proteosome. This mutation is the most common mutation of the CFTR, causing >90% of Cystic Fibrosis cases .

Class III: Altered Regulation (e.g. G551D)

Class IV: Conductance Defect (e.g. R117H)

Class V: Reduced Protein Synthesis (e.g. A455E)

Approaches to Treatment

Lung Function

Physiotherapy and mucolytics

Oral and Inhaled Antibotics

Anti-Inflammatory Drugs

Lung Transplant

Gene Therapy

Pharmacotherapy

Alternative Channel Therapy

Pancreatic Function

Pancreatic Enzyme Replacement

Nutrional Regime