ABSTRACT
Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) have been show to cause CF, and provide a molecular basis for the defective cAMPmediated salt and water transport across epithelial tissues.4-6
Introduction 297 Clinical background 298 Mutation analysis and genotype-phenotype correlations 302 Animal models 303 Modifier studies in humans 304
Disease management/future developments 306 Other genetic causes of bronchiectasis 306 Young syndrome 306 References 307
Figure 11.1 Organ systems affected in patients with CF. Patients with CF have disease manifestations in epithelial tissues of many organ systems. Individuals with classic CF have manifestations in each of the organ systems shown below, whereas patients with nonclassic CF have symptoms in a limited subset of these
Genotype-phenotype studies have revealed that disease in some organ systems is correlated with CFTR genotype (e.g., the pancreas), whereas in other organ systems (e.g., the respiratory tract) variability in severity seems to be influenced by factors other than CFTR genotype such as environmental exposure or genetic background.7-10 These findings have fueled the search for additional genes that modify the severity of the CF phenotype.11-13 In this chapter, we will summarize our current understanding of the molecular pathophysiology of CF.
