kind of CF

Question

My husband and I are carriers of delta F508 en N1303K.
To what kind of CF this combination of mutations can lead?
Assembly or not of the CFTR channel? And is it broken down or not afterwards?

Answer

Thank you for your question.

The severity of CF is partly determined by the type of mutation in the CFTR gene. Mutations (= small genetic errors) in the CFTR gene lead to disturbances in the assembly and function of the CFTR protein. This protein functions as a channel in the cell surface and is responsible for the transport of salt (chloride ions).

The mutations are divided into five categories. Each CF patient carries 2 mutations, not necessarily from the same class.
In class 1 mutations, there is no CFTR channel. In class 2 mutations an abnormal CFTR channel is made that is broken down before it arrives at the cell surface. In class 3 mutations, the CFTR channel is produced and is integrated into the cell surface, but it cannot be activated. In type 4 mutations, the channel is too narrow and type 5 mutations leads to production of a smaller number of channels, but with normal function.

F508del and N1303K are both type 2 mutations. This means that nearly all CFTR channels are broken down and hardly any make it to the cell surface.

Patients with 2 mutations of class 1 to 3 usually present with severe disease. This is thus also expected for the combination F508del and N1303K: classic CF symptoms with lung disease from early life, maldigestion, fatty stools, a clearly abnormal sweat test and male infertility. Additional complications such as diabetes and liver problems may occur in adulthood.

But there is a great variability in lung disease severity between patients having exactly the same mutations. Other genetic factors ( called modifier genes') and environmental factors (such as age at diagnosis, intensity of treatment and exposure to smoke) also determine disease severity.

Although we know much about patient groups, it remains very difficult to make a good prediction for an individual patient.

I hope your question has been answered sufficiently.
Best regards,
Prof. Dr. K. De Boeck

06.05.2013