F508del heterozygoty : consequences?

Question

Hello,
I am a 32 year old male in pretty good health, out of curiosity and I did a genetic test through a U.S. site.
Among the many results I found to be heterozygous for deltaF508 carrier (30 other mutations investigated, all negative)
I read many articles and abstracts of publications, and it made me make a connection with my symptoms and which remained unexplained:
- Frequent cough just after the meal time since sometimes
- Seasonal bronchitis that required tough antibiotics (I am non-smoker)
- And especially has always been constant presence of mucus in the back of the nose / throat and constant need to sniff / swallow / clear my throat, to the chagrin of those around me.

Note that my father had the same respiratory symptoms and, moreover, had some problems before having children (made ​​of a varicocele)

I am concerned primarily with my fertility. I also had a varicocele. I think a lot of figures on the frequency of deltaF508 in people with CABVD, but never the reverse. I read that "5T allele" is found frequently in these cases, but does not know where to find it in my results (I can search by number of SNPs)

I also wonder if there is no preventive things to ENT and Respiratory side, because I feel that my bronchitis are more severe than some years ago. And monitor my pancreas.

Who consult for a first time ? A GP (I fear it does not take very seriously my test or not at the forefront of the subject)? A pulmonologist and a urologist separately?
Or direct a specialized muco would have all these skills?

NB: I live in England but often returns to France.
Thank you!

Answer

Hello,
It is not a good idea to do molecular genetic testing without medical counselling and most often ther is more confusion than enlightening and the efforts necessary to clarify such issues frequently are quite very bothersome, costly, and unfavourable. In most cases the confusion is bigger than the clarification.
CF is a so-called autosomal-recessive disease, i.e. only if there is a mutation in each CFTR-gene on both chromosomes of the chromosome pair no.7, the patient suffers from cystic fibrosis. Subjects heterozygous for DF508 mutation (having only the DF508 mutation on one chromosome and the other chromosome carries no CFTR-mutation) are usually asymptomatic for any symptoms and with normal fertility status as it is the genetic profile of parents of most cystic fibrosis patients. Some studies have been performed concerning the health of parents of children with CF as an example of healthy carriers of just one CFTR-gene mutation. In summary, based on current knowledge, the parents of children with CF are generally well and deserve their name of "healthy carriers". They are not at risk of developing severe respiratory impairment. However, mild respiratory or mild ENT symptoms may be a little more frequent. "Varicocele" is not associated with CF mutations.
However, there is the very small possibility, that a person like you where only one mutation has been identified might carry a CFTR-mutation on the other chromosome that has not been detected by the genetic screening; the test that has been performed in your case did only test for the 30 most frequent mutations (when the test is performed in the Us, this is the frequency spectrum there and not in a Europid population). In such a case, one might speculate that such a proposed second mutation would not be a classical “CF-causing” mutation (as you are otherwise healthy) but could lead to a very mild form of CF-like disorder, probably only causing fertility problems.
Concerning the fertility issue, you should at the moment not need to worry about this, as there is nothing that can be done in advance to improve a possible problem later. It is most likely, that you will have no fertility problems due to the underlying CFTR-mutation at all. So if you come later to the concrete situation of family planning, you might have a spermiogram done at e.g. a specialized urologist/endocrinologist. In the situation of family planning, it would also be advisable to have a genetic counseling before any procreation: if your partner is also heterozygous for CF there is a 25% risk to have a CF child together.
There is no necessity to have pancreatic investigations. For your respiratory symptoms please see a pneumologist or ENT-specialist who are competent for it to judge if the symptoms are so severe that they deserve further investigations. As you stated that you were not a smoker I do not have to mention that any use of tabacco has to be avoided.
Pr Isabelle Durieu, Pr TOF Wagner and Dr. D. d’Alquen

16.12.11
Dear All,
As Pr Durieu did not agree with this response, I did the translation in French and posted it.
I will inform the questioner.
All the best and happy holidays,

Dr Sophie Ravilly

13.12.2011