Molecular Testing for Cystic Fibrosis and CFTR-Related Conditions

Publisher Summary This chapter discusses the molecular testing for cystic fibrosis and conductance regulator (CFTR)–related conditions. Classic CF is defined as a triad of progressive obstructive lung disease, pancreatic exocrine insufficiency, and malformation of the male reproductive tract, usually manifested as congenital absence of the vas deferens. The CF transmembrane (CFTR) gene was identified as the cause of CF 20 years ago. Since that time, over 1,500 mutations have been identified in the gene, although only a small fraction account for most of the CF-causing alleles. Molecular diagnosis of CF in a patient with suggestive clinical features involves a stepwise process of testing for common alleles and, if necessary, extensive gene analysis. Screening of healthy members of the general population for CF carriers is generally restricted to a mutation panel that detects approximately 85% of CF-causing alleles in Caucasians. CFTR genotype is predictive of pancreatic exocrine function. However, CFTR genotype is of minimal utility for predicting survival due to the prominent role of genetic and environmental modifiers for lung disease, the major cause of morbidity and mortality.