Combination deltaF508 and R117H-T7

Question

Dear ladies and gentlemen,

My friend and I are carriers of above mentioned combination. We are busy with a PGD (preimplantation genetic diagnosis) process in order to exclude CF but we are also busy with this issue. What if the PGD does not succeed? What actions do we have to take then? We will almost have our third chance.
Ending the pregnancy after an amniocentesis in case of CF is one of the possibilities, but not an easy one....
At first we have been told that the risk of a classical form of CF would not be great. Rather the child would have a mild form of CF or no symptoms at all.
Can you tell me something about the combination of mutations in the CF-gene? What is the truth?
Is it true that the chance of having a child with a classical form of CF is so small that we have to ask ourselves if, for example, to terminate the pregnancy in case of a shown CF is a good decision?
Many thanks in advance

Answer

Thank you for your question.

On this website, we can only provide you with some general information about these CF mutations.

Cystic fibrosis (CF) is caused by mutations (bugs) in the CFTR - gene. Each individual has two CFTR genes: one inherited from the father, the other from the mother. Only when a disease causing mutation is present on both CFTR genes, you have CF.
The most difficult point is to distinguish a gene anomaly which causes a disease (a mutation) from a gene anomaly which can be considered as a variant. You describe the combination of F508del and R117H in combination with 7T. The first (F508del) is definitely a disease-causing mutation. For the second (R117H 7T) this much less clear.
Initially, the R117H mutation was considered as a ‘mild' mutation. Typical for mild mutations is indeed that patients have normal digestion, only mild lung or sinus problems, but possibly problems with male fertility due to absence of the vas deferens. Later it became clear that the R117H mutation also occurs in people without symptoms and in men with only an absence of the vas deferens. This variability is in part explained by the presence of a T5, T7 or T9 variant in combination with R117H: the longer the T tract, the less likely symptoms occur.
Especially in the French screening programme, where newborns are systematically screened for CF, many children with mutations R117H-T7/F508del with no CF symptoms were found. Lung problems at young age in patients with delF508 and R117H/T7 are very rare. A very recent French report (Jan 2012) shows that R117H/T7 in combination with a CF mutation only causes in 0.03% of the cases a real CF disease (and in adults only 0.06%).

Hopefully we could clarify your question with this answer. As you are in a fertility process, we suggest that you discuss this issue specifically with your doctor.

Best regards,
Prof. Dr. K. De Boeck

06.05.2013