Research into cystic fibrosis is revising what scientists and doctors originally thought about this disease.
It is well-known that cystic fibrosis is a recessive, genetic disease, the most common life threatening genetic disease in countries like the USA, UK and Australia. Research has focused on a gene called the CFTR (or cystic fibrosis transmembrane conductance regulator) gene. This was found to be the ‘cystic fibrosis gene’ in 1989. Since then many other genes have been found that change the symptoms of cystic fibrosis. These are called ‘modifier genes’.
A New Piece of the CF Puzzle
Now another piece of the cystic fibrosis puzzle looks like it may have been found that relates to the job of the CFTR gene and how it creates the symptoms of cystic fibrosis. It was originally thought that role of CFTR related to the movement of naturally occurring ion in the body that is needed for normal health – chloride. This theory made cystic fibrosis a disease of chloride dysfunction. Yet there was a puzzling finding appearing in scientific research that some disease-causing cystic fibrosis mutations (such as H620Q and A800G, two of nearly 1,900 different mutations) actually increased the chloride function of CFTR. They should not have created any symptoms according to the chloride theory.
This puzzling finding led researchers to the discovery that the CFTR gene controls more than just chloride in the body – it is also vital for bicarbonate functioning. Bicarbonate is naturally made by the body and is essential because it prevents the body from becoming too acidic.
A New Theory for CF
The research now suggests that the traditional belief about chloride and cystic fibrosis is outdated. This is because scientists have found that things are far more complex. Instead of all the 1,900 cystic fibrosis mutations known to occur on the CFTR gene creating disease in the same way they are all unique. Some only create problems with chloride functioning (like the mutation G551S). Others only create problems with the bicarbonate functioning (like R75Q). Whilst other mutations change both chloride and bicarbonate functioning but in a different way. The mutation R117H acts in this way by decreasing chloride function by 70% and bicarbonate functioning by 37%.
Now what does this mean for families and medicine? Firstly it suggests the ‘sweat test’ which was once considered the best test for cystic fibrosis is now outdated. Why? Because it does not test bicarbonate levels and will miss people with cystic fibrosis due to mutations that decrease the bicarbonate functioning only. The role of bicarbonate also gives science information that helps explain why people with cystic fibrosis have thick, sticky mucus. The improper functioning of bicarbonate in areas like the lungs makes things to acidic which in turns increases the thickness and stickiness of the mucus. Finally, and most importantly a scientific finding like this holds hope for better medications to treat cystic fibrosis and hopefully give a cure in the future.
For More Information See:
A Diagram from the journal Nature that explains this.
A News Item "Researchers Link Bicarbonate Transport to CF"
Another News Item "Bicarbonate Linked to Sticky Mucus in CF"
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