The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene provides instructions for making the CFTR protein. Genetic mutations are changes in a gene’s DNA sequence. When these changes occur in the CFTR gene, they can affect the production, structure, or function of the CFTR protein, impacting the body.
The Role of the CFTR Protein
The CFTR protein functions as a channel on the surface of cells that produce various fluids, including mucus, sweat, saliva, tears, and digestive enzymes. Its primary role involves regulating the movement of negatively charged chloride and bicarbonate ions across cell membranes. This transport of chloride ions helps control water movement in tissues, necessary for producing thin, freely flowing mucus.
Beyond chloride, the CFTR protein also regulates other channels, such as those transporting positively charged sodium ions across cell membranes. Maintaining this balance of ions and water is important for proper fluid consistency in various bodily systems. When the CFTR protein functions normally, it ensures mucus remains of normal consistency in airways, the digestive system, and other organs.
How CFTR Mutations Affect the Body
When the CFTR gene is mutated, the resulting protein may be non-functional, work less effectively, break down too quickly, or be present in insufficient amounts. These alterations disrupt the normal flow of chloride ions and water in and out of cells. Consequently, cells lining passageways in the lungs, pancreas, and other organs produce mucus that is abnormally thick and sticky.
This mucus can obstruct airways in the lungs, leading to difficulty breathing and recurrent respiratory infections. It can also clog the digestive system, particularly the ducts in the pancreas, impairing the release of digestive enzymes needed for nutrient absorption. This can result in malnutrition and weight gain issues.
Other organs can also be affected by the impaired CFTR protein. The liver may experience blockages in its ducts, and sweat glands produce sweat with an unusually high salt content because chloride is not reabsorbed properly. The specific type of CFTR mutation can influence the extent of protein dysfunction and the severity of symptoms.
Inheritance of CFTR Mutations
CFTR mutations are inherited in an autosomal recessive pattern. This means an individual must inherit two mutated copies of the CFTR gene, one from each parent, to develop the condition. If a person inherits one mutated CFTR gene and one normal copy, they are considered a “carrier.” Carriers do not display symptoms because their one functional copy of the gene is sufficient for normal protein function.
When two carrier parents have a child, there is a 25% chance (1 in 4) that the child will inherit two mutated copies and develop the condition. There is also a 50% chance (1 in 2) that the child will inherit one mutated copy and one normal copy, becoming a carrier themselves. Lastly, there is a 25% chance (1 in 4) that the child will inherit two normal copies of the gene and neither have the condition nor be a carrier.
Detecting CFTR Mutations
Detecting CFTR mutations begins with newborn screening. This screening involves a blood test checking for elevated levels of immunoreactive trypsinogen (IRT), an enzyme precursor from the pancreas that is high in babies with the condition. Since elevated IRT can have other causes, a high IRT level prompts further testing.
Following a positive newborn screening, a sweat chloride test is performed, a standard for diagnosis. This test measures the concentration of chloride in sweat.
Genetic testing, which involves analyzing DNA from a blood or saliva sample, can directly identify CFTR mutations for diagnosis or carrier screening. This helps confirm a diagnosis or assess an individual’s carrier status.