Chapter 14, Problem 23PDQ

Cystic fibrosis (CF) is a severe autosomal recessive disorder in humans that results from a chloride ion channel defect in epithelial cells. More than 500 mutations have been identified in the 24 exons of the responsible gene (CFTR, or cystic fibrosis transmembrane regulator), including dozens of different missense mutations, frameshift mutations, and splice-site defects. Although all affected CF individuals demonstrate chronic obstructive lung disease, there is variation in whether or not they exhibit pancreatic enzyme insufficiency (PI). Speculate as to which types of mutations are likely to give rise to less severe symptoms of CF, including only minor PI. Some of the 300 sequence alterations that have been detected within the exon regions of the CFTR gene do not give rise to cystic fibrosis. Taking into account your knowledge of the genetic code, gene expression, protein function, and mutation, describe why this might be so.