Genetics Disorder Assignment
By Arian and Phantira
SBI4U - Block 5: Protein Synthesis
Cystic Fibrosis, an autosomal recessive is caused by the mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene, located on the long arm of chromosome 7.
The CFTR protein is an adenosine triphosphate (ATP)-binding cassette (ABC) transporter. The CFTR protein is located in the apical surface of airway, intestinal, and exocrine epithelial cells and primarily functions as a transporter of chloride and bicarbonate ions. This channel secretes chloride and bicarbonate into the lumen and modulates reabsorption of sodium and water by the epithelial sodium channel.
Other functions of the CFTR protein are located in the lungs where it ensures optimal volume, electrolyte composition, and pH of the airway surface liquid (ASL), a thin fluid layer protecting the epithelium from inspired air.
Not all mutations of the CFTR gene will cause Cystic Fibrosis, many of these mutations will only lead to CFTR-related disorders (CFTR-RD).
Cystic Fibrosis causing mutations are generally divided into five different classes, according to the molecular and functional defect engendered. The sixth class had recently been added, but it is yet poorly described according to scientists.
- Class I - Mainly caused by premature stop codons (non-sense mutations), but also includes canonical splice mutations, and chromosomal deletions.
- Class II - A three base pair deletion results in a missing amino acid causing CFTR protein to be unable to reach apical cell surface. Most frequently encountered (90% of European and American Cystic Fibrosis patients). A common class II mutation is Phe508del.
- Class III - Deregulated opening function in the channels of a normal CFTR protein (gating mutations). Opening time of channel gate is reduced which does not allow sufficient passage of chloride anions.
- Class IV - Reduced chloride conductance in a normal CFTR protein (inefficient electrolyte transport occurs even when the channel is open).
- Class V - intron mutations which affect splicing and reduce CFTR synthesis.
- Class VI - missense mutations result in an unstable protein.
Further complications are found in some CFTR alleles that encompass two distinct mutations, also called complex alleles. This results in an effect that is even more difficult to predict.
When CFTR is dysfunctional, transmembrane movement of chloride is impaired, resulting in thick, sticky mucous secretion in the digestive tract and in the respiratory tract, which clogs the airways in the lungs and increases the risk of infection by bacteria.
- coughing with productive thick mucous
- wheezing and shortness of breath
- respiratory illnesses (such as pneumonia or bronchitis)
- weight loss or failure to gain weight despite possible increased appetite
- salty-tasting skin
- bowel disturbances, such as intestinal obstruction
- greasy stools.
There is no cure for cystic fibrosis yet, but new treatments are helping people with the disease to live longer. Common treatments include:
- Chest physical therapy, in which the patient is repeatedly clapped on the back to free up mucus in the chest
- Inhaled antibiotics to kill the bacteria that cause lung infections
- Bronchodilators that help keep the airways open
- Pancreatic enzyme replacement therapy to allow proper food digestion
- Jensen, K. (2005). Cystic fibrosis. Alive: Canada's Natural Health & Wellness Magazine, (271), 64.
- Kirkpatrick, I. D., & Greenberg, H. M. (2002). Answer to case of the month #85: Abdominal computed tomographic manifestations of cystic fibrosis in an adult. Canadian Association Of Radiologists Journal, 53(2), 103.
- Meng, S., Yong, G., Yingying, Z., Korteweg, C., & Jiang, G. (2010). Expression of cystic fibrosis transmembrane conductance regulator in paracervical ganglia. Biochemistry & Cell Biology, 88(4), 747-755.
- Sanz, J., von Känel, T., Schneider, M., Steiner, B., Schaller, A., & Gallati, S. (2010). The CFTR frameshift mutation 3905insT and its effect at transcript and protein level. European Journal Of Human Genetics, 18(2), 212. doi:10.1038/ejhg.2009.140
- Vallières, E., & Elborn, J. S. (2014). Cystic fibrosis gene mutations: evaluation and assessment of disease severity. Advances In Genomics & Genetics, 4161. doi:10.2147/AGG.S53768