Cystic Fibrosis

Question 1

What is the prevalence of CF? What is the most common mutation and what are the different mutation classes?

Answer 1

1 in 3200 in NZ, most common life limiting recessive trait among white people. AR, >15000 gene mutations at single locus 7q (CF gene), 230 mutations in the CFTR gene 70%delta F508.

CFTR expressed in Ep cells airways, GIT, sweat glands, GU. class 1 to 5. Class 2 most common (70%), protein produced but not trafficked to apical membrane, deletion of single phenylalanine at delta 508.

Question 2

How does % of loss of CFTR activity relate to severity of clinical features in CF?

Answer 2

99%loss = lung disease and panc insuff
95% loss = lung disease (retain panc fxn)
90% = isolated congenital absence of vas def or idiopathic pancreatitis

Question 3

List 3 mutations associated with more severe phenotype in CF

Answer 3

Single nucleotide change in TGF-b1
Variant alleles of mannose binding lectin
Polymorphism in the IRFD-1 gene