Extended cystic fibrosis testing - does the end justify the means?

Introduction Mutation testing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is often required for a definitive diagnosis of cystic fibrosis, but >1000 mutations are known. Aims To compare the mutation detection rate of our in-house 11-mutation panel against a 33-mutation panel and direct gene sequencing in patient groups stratified by sweat test (SWT) status. Methods All clinically diagnosed cystic fibrosis (CF) patients presenting between 2003 and 2007 were reviewed to determine their SWT results and CFTR genotypes as identifiable by sequencing, the 11-plex screen or the Abbott-Celera 33-plex oligonucleotide ligation assay (OLA) kit. In total, 85 patients in total were analysed. Results 56% of SWT positive patients were fully characterised by the 11-plex screen, compared with 62% by 33-plex screen and 85% by sequencing. The detection rate was substantially lower in SWT equivocal/negative patients (16% by 11-plex, 21% by 33-plex, 58% by sequencing). Ten of 66 SWT positive patients remained incompletely genotyped even by sequencing, while 11 of 19 SWT equivocal/negative patients carried 2 mutant CFTR alleles. Discussion The 33-plex screen offers improved detection rate over the 11-plex screen but sequencing remains necessary for a substantial proportion of patients. Negative SWT or negative sequencing alone should not be taken to exclude CF.