Review Question - QID 106523

The most common mutation in cystic fibrosis is the 3-base pair deletion in the CFTR gene that removes phenylalanine at amino acid position 508.

Cystic fibrosis is the most common lethal genetic disease of the white population. It is caused by an autosomal recessive defect in the CFTR gene on chromosome 7. The most common mutation is a 3-base pair deletion that removes phenylalanine at amino acid position 508. This mutation causes defective post-translational folding and glycosylation, resulting in degradation of the CFTR channel before reaching the cell surface. The CFTR gene codes for the CFTR channel which actively secretes Cl- in the lung and GI tract and actively reabsorbs Cl- from sweat. This defective Cl- channel causes secretion of abnormally thick mucus that plugs the lungs, pancreas, and liver and leads to the variety of symptoms seen in CF, including recurrent pulmonary infection, pancreatic insufficiency, as well as failure to thrive and meconium ileus in newborns. Of note, due to routine screening almost all cases of CF are diagnosed at birth. However, the diagnosis could be missed in patients born outside of the healthcare system as in this patient.

Sawczak et al. describe novel therapeutic approaches in treating cystic fibrosis. They state the ultimate goal of treatment should be to correct dysfunctional CFTR proteins in CF patients. To that end, they state that S-nitrosothiols (SNOs), small naturally occurring endogenous cell signaling compounds, may possibly increase CFTR maturation and function at the plasma membrane in human airway epithelial cells. However, clinical trials are still investigating the effectiveness and safety of these compounds.

Grosse et al. review the CDC guidelines for newborn screening for cystic fibrosis. The CDC currently recommends routine screening of all newborns for cystic fibrosis. This should be accompanied by rigorous infection control practices to minimize the risk to children with cystic fibrosis detected at an early age of acquiring infectious organisms associated with lung disease from older patients. Education of parents should play an important role in any screening programs.

Illustration A depicts the effects that the thick mucus in CF has on the lungs and digestive tract. Illustration B demonstrates the effect of the CFTR mutation on the CFTR channel in CF.

Incorrect Answers:
Answers 1-4: None of these amino acids are the most commonly deleted amino acid in the CFTR gene in cystic fibrosis. Rather, deletion of phenylalanine is the most common.