genetics

Question

In my 5-month-old daughter CF was diagnosed and mutations 3849+10kbC>T/2143delT were detected. I can't find any information about the second mutation. So far my daughter has no symptoms. On the basis of these mutations, can one predict the course of the disease: mild or severe?

Answer

Dear questioner,
In general it has to be stated, that the course of the disease of CF in the individual patient is affected by the genetic findings (types of mutation as you mentioned in your question) but as well by other genetic and environmental factors. Therefore, even if trends of the severity of the disease can be made out of the genetic constellation, to give a precise prognosis of the individual patient is not possible.
As every human being has two copies of each gene and CF belongs to the so-called “autosomal-recessive” disorders, two mutations in the CFTR-gene (which is responsible for causing the disease of CF) are necessary in order to suffer from this disease (only one mutation leads to healthy carriership). If two mutations in the CFTR-gene are present (as in your special case, too) the clinical outcome is determined by the less severe mutation. Your daughter carries the two mutations 3849+10kbC>T and 2143delT. 2143delT belongs to a class of mutations leading to the “typical picture” of CF with lung disease and pancreatic insufficiency. However, this is not of great relevance for your daughter, as she carries also the mutation 3849+10kbC>T, which belongs to a less severe class of mutations and is therefore deciding for the clinical picture of your daughter. This mutation is usually associated with milder lung disease and pancreatic sufficiency. However, this special mutation has a specialty; it is a mutation which can have a variable disease expression ranging from minimal lung disease, pancreatic sufficiency and male fertility to a relatively severe disease in all involved organs. Therefore a precise prognosis is not possible even if chances are great that the course of the disease will be a mild one.
If you have further questions it could be of advantage to contact a genetic center for genetic counseling.

First and foremost one should remember, that CF is a chronic and progressive disease, but proper treatment and physiotherapy are of the greatest importance to disease course.

Best regards,
prof. dr hab. med. Wojciech Cichy
dr n. med. Natalia Kobelska-Dubiel
(consultation: dr n. med. Agnieszka Sobczyńska-Tomaszewska)

14.04.2010