Cystic Fibrosis Mutations

The genetic mutation that causes Cystic Fibrosis was discovered in 1989. Mutations on a single gene- the Cystic Fibrosis Transmembrane Regulator (hereafter referred to as CFTR) causes the most common, fatal genetic disease.

Since the discovery of the CFTR gene, researchers have identified over 1,800 mutations. These mutations are grouped into different classes and types dependent upon how the mutation affects the key protein produced by the CF gene.

The CFTR gene is located on the 7th chromosome and is composed of 250,000 DNA nucleotides. In healthy people (those with normally functioning CFTR genes), the CFTR is located on the surface of the cells that line the lungs and other organs. The protein made by the CFTR is a chloride channel. Chloride flows in and out of the cells through a "doorway" and water flows behind in. The water keeps the mucus this and moves it out as well.

What is a nucleotide?
A structural components of DNA and RNA. A nucleotide consists of one of the following chemicals: adenine, thymine, guanine, or cytosine, plus a molecule of sugar and one of phosphoric acid.

What does the CFTR gene do?
The CFTR protein functions as a channel for the movement of chloride ions in and out of our cells. This is important for the salt and water balance on epithelial surfaces (the tissue that lines the cavities and surfaces throughout the body). A balanced level is highly important for the lungs and pancreas, however, due to mutations of the CFTR, these organs are negatively affected. The mutations affect the composition of the mucus layer (airway surface liquid, ASL- a liquid and mucus gel layer that contains salt) that lines the epithelial surfaces in the lungs and pancreas. A disruption in of ion transport affects the salt concentration in the sweat. This is why sweat tests are used as a diagnostic measure.

Although a diagnosis of Cystic Fibrosis is usually straightforward, genetic testing is preferred. Genotype is not the final arbiter of a clinical diagnosis of CF. Diagnosis is primarily based on: sweat testing, nasal potential difference, and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF.

In order to Cystic Fibrosis, a person must have inherited two defective genes from both parents. The mutations can be the same (homogenous) or different (heterogenous). For example, a person could have the 621+1g>t mutation and the F508del mutation. The heterogeneity of CFTR mutations in various populations makes mutation detection rates extremely challenging. A small number of CF patients have only one or no CFTR mutations identified.

Why do mutations matter?
Not every case of Cystic Fibrosis is the same. A CF Patient's mutation determines what happens on a cellular level.

Identification of the underlying mechanisms that cause CF allows for researchers to better understand how certain medications can help specific CF patients. CFTR targeted therapies could treat the issues on a cellular level, which would address the cause of CF as opposed to the symptoms of CF.