PSC2002/L07 Cystic Fibrosis I Flashcards
What kind of disease is cystic fibrosis?
Autosomal recessive
What is cystic fibrosis caused by?
Loss-of-function mutations in Cystic Fibrosis Transmembrane Conductance regulator (CFTR) gene
What is regulated by the CFTR channel? (2)
Volume
pH
-of epithelial secretions
How does CF present?
Severe lung & pancreatic disease
Affects multiple organs including GI and reproductive tracts and sweat glands
What percentage of morbidity and mortality foes CF lung disease account for?
90%
Give 3 statistics about CF.
> 11,000 people with CF in UK
150,000 worldwide
In UK, 1/25 people are carriers
In 1964, median life expectancy was 5 years; is now >50
Females have lower life expectancy than males
CF screening started in 2007
How many mutations and disease-causing mutations have been identified for CF?
> 2000 mutations
720 disease-causing mutations
What are the most common CF mutations?
50% of pwCF homozygous F508del
35% pwCF compound heterozygous (F508del/G542X)
5 other mutations have >1% frequency
Describe type I CFTR mutations.
No protein produced
E.g., G542X
Describe type II CFTR mutations.
No traffic of protein to Golgi or apical membrane
E.g., F508del
Describe type III CFTR mutations.
Normal protein level but channels don’t function normally
E.g., G551D
Describe type IV CFTR mutations.
Single channel conductance reduced (less function)
E.g., R117H
Describe type IV CFTR mutations.
Less protein produced
E.g., A455E
Describe type VI CFTR mutations.
Less stable protein
Lower half-life so channels broken down more quickly
No example required
Describe genotype-phenotype relationship.
Whether disease severity (phenotype) can be predicted from mutational analysis (genotype)
