1.
Group 1 mutations: In mutations in this group, the "stop" codon occurs early as a result of nucleotide change. This causes the protein produced to be a short KFTR protein with the missing number of nucleotides. As you can imagine, this short protein often fails to function.
2.
Group 2 mutations: Although our KFTR protein is formed in this group, there is a problem in intracellular traffic and the formed protein cannot reach the cell membrane. Unable to reach the membrane, the protein breaks down inside the cell.
3.
Group 3 mutations: In this type of mutation, although the KFTR protein is formed and even transmitted to the cell membrane, Cl passage cannot be achieved because the channel is not opened
4.
Group 4 mutations: In this group, our protein has been formed, transmitted to the cell membrane, and the door of its channel has been opened. However, due to the conduction disturbance, there is much less Cl transition than normal.
5.
Group 5 mutations: Everything is fine in this group, but the amount of protein produced is less than normal. For this reason, there is less Cl transition than it should be.
6.
Group 6 mutations: In this type of mutation, our protein has formed and reached the membrane, but since its stability is low, it leaves the membrane in a short time and breaks down inside the cell.
7.
Group 7 mutations: In the last type of mutation, mRNA cannot be formed due to large deletions in DNA. This is the most difficult type of mutation to treat.
What is Cystic Fibrosis ?
Whenever we breathe, we constantly ingest bacteria and viruses from the air. So why don't we get sick despite this? Because we have amazing protection systems in our air gaps!
Our air spaces are covered with a tissue we are all familiar with called mucus. Our body wastes such as sputum and mucus, which we all know very well, are also mucus. So why is mucus so important?
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We can compare the function of mucus in our body to the function of oil in an engine. Mucus also provides the moisture of the surface of our organs, it kind of lubricates our organs. It facilitates our breathing, prevents the stomach from digesting itself and prevents bacteria from damaging the teeth. It allows us to chew food more comfortably. In addition to these, mucus has a very important task, which is to capture bacteria and viruses and expel them from our body by the action of the cilia. So what is the condition of mucus in Cystic Fibrosis patients?
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Cystic Fibrosis disease occurs when this mucus layer in our body hardens and therefore cannot be removed from our body. In other words, even if mucus succeeds in catching bacteria, which is its most important task, it cannot be eliminated from our body. For this reason, these microbes remaining in our body cause inflammation. But that's not the only problem. This hardened mucus layer can accumulate and block the airway. Which means being unable to breathe. The cilia, which cannot move due to the solidified mucus layer, prevent the different secretion mechanisms in our body from working properly. For example, bile fluid secreted from our pancreas, which allows us to digest fats, cannot function and patients become unable to digest fats. Therefore, deficiency of fat-soluble vitamins A, D, E, K is also observed. We will share other symptoms caused by the disease in detail in a different article.
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Let's talk a little about the mechanism of the disease. We realized that the structure of mucus in Cystic Fibrosis patients is stricter than normal. So what is the reason for this?
The Cystic Fibrosis gene is located in the q22-31 region of chromosome 7. This gene encodes the cystic fibrosis transmembrane regulator (KFTR) protein found in many of our cells. So what is the task of this protein?
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KFTR protein functions as the Cl- ion channel in cells. Due to the malfunction of this protein, Cl- ion cannot pass between cells. As a result, Cl- that needs to be separated from the cell cannot be separated from the cell, and Na + ion accumulates in the cell. As a result of all this, the water inside the cell cannot leave the cell, thinning the tissue of the mucus and moisturizing the mucus. For this reason, mucus becomes solid and moisture-free.
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So what causes the dysfunction in the KFTR protein?
Of course, from the gene that encodes that protein! The mutations in the KFTR gene in the 7th chromosome we just mentioned cause a loss of function in the protein produced by this gene. Approximately 2000 types of mutations have been detected in the KFTR gene so far. If we need to examine this mutation under 7 different categories explained in the table at the left
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The most common mutation in the KFTR gene is ∆F508. This corresponds to the 2nd group. The incidence of this disease in the white race is 1 in 3000, 82.4% of this disease in Europe has the F508 mutation. In other words, the reason for the dysfunction in the CFTR protein in most of the patients is that there is a problem in the transport of this protein to the cell membrane.
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In this article, we talked about what Cystic Fibrosis disease is and what mutations it is caused by. In our next articles, we will talk about the symptoms and treatment methods of the disease. Don't forget to follow us on our social media accounts!
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Rüya Aslan
