The expected level of illness

Question

Dear reader,

My husband and I are carriers of the CF gene. It concerns Delta F508 and N1303K.
What can you say about the health of our future child if the child carries both mutations and has CF in that case?

(we know that the chances are 25% in case of natural conception)

I look forward to your answer.

Sincerely,
L.

Answer

Thank you for your question.

The severity of CF is in part determined by the type of mutation in the CFTR gene. Although more than 1900 different mutations are known, these are divided in 5 categories according to their effect on the CFTR protein production or function. Class 1 mutations lead to hardly any protein present. Class 2 mutations contain an error and protein is broken down by the cell quality control mechanism. Both DF508 and N1303K belong to this class 2. In class 3 the protein is there but it doesn’t open. In class 4 protein is there but it is structurally abnormal. In class 5 there is protein but not in sufficient amount.
Patients in whom both mutations belong to class 1 to 3 have the severe form of disease. This implies: symptoms from early after birth with airway infections as well as maldigestion due to pancreatic insufficiency. However, even if patients have 2 severe mutations there is great variability between patients. This is because other genetic factors and environmental factors also determine the disease severity.
To summarize: in case a child would have a combination of DF508del and N1303K it is expected to have a severe form of CF with airway infection and malabsorption from early life on. There is however great variability in the exact disease severity in these persons. We hope that this anwers your question

Prof.Dr. De Boeck

25.09.2012