Cause of CF

Question

Hello, what is the exact cause of cystic fibrosis?

Answer

First some general information. The genetic code for all proteins that our body has to make is stored ‘as a model’ in the genetic material of every cell of our body. This information is stored in the genes on the chromosomes. If a specific protein needs to be made this code is then transcribed and translated to a protein by specific machinery in the cell. Every protein has a specific function. The CFTR protein functions as a chloride (i.e. salt) transporter. An error in the code of the gene on the chromosomes will lead to poor or no function of a specific protein. Such a person suffers from a genetic disease because he can also transmit this error to his descendants. Cystic fibrosis is caused by an error in the CFTR gene which is one of the protein channels regulating the salt transport in the cells of the lung. If it is not functionning the fluid lining the airway surface dries out.
Cystic fibrosis is an autosomal recessive disease. Autosomal means that inheritance is independent of the sex and occurs equally frequent in boys and girls. Recessive means that somebody who suffers from cystic fibrosis inherited an error in the CFTR gene from both his parents and does not have a normal copy of the CFTR gene. Because there is an error on both copies of the CF genes there is very little or no normal CFTR protein made. The CFTR protein is present in the cells of every organ of the body but is most important in the lungs, the pancreas, the gut and sweat gland.

CFTR functions as a chloride channel and brings chloride (the negative part of salt) from the inner part of the cells outward. CFTR also slows down the function of the sodium channel that transports sodium (the positive part of salt) from the outside to the inside. Somebody with CF has very little chloride pumped out of the cell and exaggerated uptake of sodium into the cell. Salt will always attract water, so insufficient salt on the outside will mean insufficient water and thus sticky secretions on the outside.

In CF the layer of fluid lining the cells in the lung is too small so that the cilia (little brushes) that extrude from the cells and are supposed to brush all debris out of the lungs cannot perform their task. Therefore patients with CF suffer from recurrent lung infections. Because of repeated infections damage happens to the lungs. This damage leads to further accumulation of sticky mucus and infection. Since the CFTR protein is necessary for the normal function of many cells in our body also problems in other organs occur such as malabsorption (insufficient function of the pancreas), liver disease, recurrent infections in the nose and the sinuses and fertility problems.
K. De Boeck, L. Dupont, M. Proesmans

26.01.2009