ABSTRACT
Since the discovery of the cystic brosis transmembrane conductance regulator (CFTR) gene in 1989, over 1900 mutations have been reported, although the contribution of many to disease is still unclear.1,2 It was anticipated that dierent mutations would correlate with dierent degrees of disease phenotypes and explain the wide spectrum of disease, but this has been only partially realized as only a small proportion of mutations correlate strongly with specic phenotypes, such as pancreatic status.3 Poor correlation between CFTR genotype and disease phenotype is most evidenced by the wide variation in pulmonary manifestations, which is particularly important as at least 90% of CF morbidity and mortality relates to pulmonary disease. For example, two individuals homozygous for the most common mutation, F508del, may have very disparate lung function and much worse prognosis as forced expiratory volume in 1 second (FEV1) is closely linked to survival.4
