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Genetic Basis Cystic Fibrosis is a progressive, autosomal recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7. The CFTR gene encodes for a protein that acts as a chloride ion channel, which regulates water and salt transport across cell membranes (Rowe et al., 2005). A mutation in the CFTR gene results in a defective chloride ion transport, leading to an accumulation of sticky and thick mucus in various organs, particularly in the lungs and digestive system (Welsh & Smith, 1993). The thick, sticky mucus build-up obstructs airways and digestive ducts. Cystic Fibrosis is inherited in an autosomal recessive manner, meaning the individual must inherit two (one from each parent) mutated copies of the CFTR gene to develop the disease (Gibson et al., 2007). There have been over 2,000 mutations identified in the gene, with the most common being F508del. This is a deletion of a singular amino acid at position 508 within the CFTR protein, accounting for roughly 70% of all CF cases (Riordan et al., 1989). The deletion of phenylalanine impairs the protein folding and trafficking to the cell surface which results in disruption of the chloride ion transport. Other mutations affect the protein in a variety of ways such as impairing its ability to conduct chloride ions or reduce its stability.
Molecular Basis Cystic Fibrosis is caused by a mutation in the CFTR gene, which encodes a chloride ion channel on the epithelial cell membrane. This gene regulates sodium and chloride ion channels crucial to maintaining hydration, thickness, and stickiness of the mucus in the lungs, organs, and pancreas (Riordan et al., 1989). The molecular basis of the disease lies in the absence or defective function of the CFTR protein which leads to abnormal ion transport at the cellular
level. Regarding the biochemical level, the absence of functional CFTR disrupts normal mucus clearance, leading to chronic respiratory infections, progressive lung damage, and airway obstruction. In the pancreas, failure to secrete digestive enzymes results in nutritional deficiency and malabsorption (Gibson et., al 2007). The molecular defect in the CFTR gene leads to abnormal chloride ion transport across cell membranes, resulting in sticky mucus being produced.
Physiologic Implications Cystic Fibrosis causes significant physiological abnormalities because of these mutations in the CFTR gene. This can lead to mild or advanced complications in individuals who have been diagnosed. In regards to the lungs, the thick and sticky mucus obstructs the airways and restricts the airflow. This also creates ideal conditions for bacterial growth, leading to chronic inflammation and infection. Constant inflammation damages the lung tissue eventually leading to bronchiectasis, a condition defined by permanently dilated airways and respiratory failure (Gibson et al., 2007). In the digestive system, the same thick mucus obstructs the pancreatic ducts, preventing any release of digestive enzymes required for the absorption of nutrients. This can lead to poor growth, malnutrition, and deficiency in vitamins such as A, D, E, and K (Dodge et al., 2013). CF also causes gastrointestinal symptoms such as abdominal pain, bloating, and fatty stools (steatorrhea). The reproductive system is also affected by Cystic Fibrosis in both males and females. CF commonly causes infertility in diagnosed males because of the congenital absence of the vas deferens, crucial for preventing sperm from reaching the ejaculate (Baker & Quinton, 2001). In females, there has also been a reduced fertility rate due to the thick cervical
Work Cited
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