Cystic fibrosis is one of the most common autosomal recessive genetic disorders among Caucasians. It is characterised by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance regulator) gene. Mutations in the CFTR gene lead to changes in the characteristics of exocrine excretions. It affects the function of the chloride ion channel which is important in creating sweat, digestive juices and mucus. An absence of functional CFTR in the epithelial cell membrane leads to the production of sweat with a high salt content and mucus secretions with an abnormal viscosity (leading to stasis, obstruction and bronchial infection).
More than 2000 mutations have been reported with the most common mutation worldwide being a three base-pair deletion, deltaF508. This results in the omission of phenylalanine at position 508 of CFTR, leading to a combination of defective intracellular processing (which results in an absence of CFTR from the membrane) and defective channel function. 31 other mutations account for a further 20% of cases.
Indication for testing
Typical CF presentation
Atypical clinical presentation and/or borderline sweat test
Male infertility with CBAVD
Other CFTR related diseases in adults
Fetusus with bowel hyperechogenicity and/or loop dilation
CF carrier testing in individuals with a positive family history
Carrier testing for oocyte donors
First option is testing for the most common F508del.
Second option is a CFTR screening assay for the common 33 pathogenic mutations (in individuals of European decent):
Delta F508 (76% White, 50% Coloured), 3120+1G→A (46% Black, 17% Coloured) and other 31 prevalent mutations (each less than 3%, 711+1G>T, 621+1G>, 1717-1G>, CFTRdele2,3(21kb) 3849+10kbC >T, 2789+5G>A, 1898+1G>A, G542X, G85E, Y1092X(C >A), G551D, R553X, 3659delC, N1303K, R560T, R117H, R1162X, L1077P, R117C, R1066C, L1065P, W1282X, R347H, R347P, I507del, T338I, I336K, 1677delTA, R334W, 3272-26A>G, 1078delT, 2183AA>G, 497, 515, 2184insA, 2143delT ,5T (9-13TG), 7T, 9T, 5T_9TG, 5T_10TG, 5T_11TG, 5T_12TG, 5T_13TG