CF yes or no?

Question

Dear,
I am a 35-year old man. Because we had problems starting a family, I had tests done. I seem to have F508del and R117H in combination with 7T/gT. Whether I do have a vas deferens? Different answer by different urologists, from ‘not present’ to ‘one sided absence’. In any case, I do not seem to have sperm in the ejaculate. We are at present doing IVF. My wife does not have any abnormalities. Of all my questions, this one is my most important one. Is this combination seen in patients with CF (mild form?) or not? Should I expect other problems in the future?

Answer

Dear Sir,
Thank you for your question.
Cystic fibrosis is caused by mutations (these are errors) in the CFTR-gene. Every individual has 2 CFTR genes, 1 inherited from one’s father, the other from one’s mother. When an error is present on both genes, one does suffer from cystic fibrosis.
The hardest is to make the distinction between changes in the gene that are OR are not disease causing. You describe the combination F508del and R117H in combination with 7T. The first one is for sure a disease causing mutation, the second one (R117H7T) is a mutation with variable consequences.
Initially R117H was considered as a mild mutation. Typical for mild mutations is that patients have no or only mild lung disease, no problems with digestion but they may have the problem of infertility. Later it was found that R117H also does occur in people without respiratory or digestive symptoms, and especially in men with absence of the vas deferens. The difference in the severity is in part explained by the presence of a 5T, a 7T or a 9T variant in combination with the R117H and only the first one, the 5T, gives a clear increased risk of cystic fibrosis.
Especially since the French (and now other) newborn screening programs, we know that many children have the combination R117H-7T/F508del and they do not develop symptoms of cystic fibrosis. Indeed, lung problems at a young age in patients with a F508del and R117H-7T are exceptional. In a recent report (Jan 2012) this combination caused a typical pattern of cystic fibrosis in children in only 0.03% of the cases and at adult age only 0.06%.
When, such as in your situation, the mutations are only associated with infertility, one does not call the disease cystic fibrosis, but CFTR-related disease. The chance that you will ever develop real CF lung problems is very small. Of course, if you do develop bronchitis or cough for a long time, you should consult a pulmonologist.
We hope that this answers your question.
Prof. Kris De Boeck

03.05.2012