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My husband was recently diagnosed positive for one copy of the R117H mutation (R117H heterozygote, homozygous for 7T). He was negative for the 5T variant. We plan to have genetic counseling. What exactly does this mean for him and for us if we have children?
Dear questioner,

Cystic fibrosis (CF) is caused by mutations 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.

In your husband, one CF-mutation, namely R117H-7T has been detected, we will come to the meaning of it later. If you are planning to have children, the probability of passing this mutation from your husband to the child is ½. In case you yourself have not been tested for CFTR-mutations, your risk of carrying also 1 CFTR-mutation is about 1/25. As you also have the chance of ½ to give this potential mutation to your child, the probability that the child inherits both CFTR-mutations from you is then 1/25 x ½ x ½ = 1/100. In case you are tested for CFTR-mutations and you are tested negative for the most common mutations, this risk decreases down to 1/400 – 1/1200 depending on the test sensitivity [1].

If your child inherits only one mutation from the father it means the child will be a healthy carrier of one CF-mutation, as your husband is and will not suffer from CF.

In the very rare case that you pass on an undetected “classical” CF mutation to your child, the R117H-7T mutation determines the severity of the illness, as it is not a “classical” CF-mutation leading to some residual functional protein.
The R117H mutation is 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 it is that symptoms occur. Therefore, R117H-7T may result in a mild form of CF, obstructive azoospermia or no disease at all [2].

In summary, if you are tested negative for CFTR-mutations, the risk is very small that the child inherits 2 CFTR-mutations and even if this should happen, in most cases there will be either no disease at all, male infertility problems or in very rare cases a mild form of CF.

We would advise you to get genetic counseling where you will get detailed information on this topic.

Best regards,
Prof Stuart Elborn
Dr. Daniela D´Alquen

1 Castellani et al. in the Journal of Cystic Fibrosis 2010, 9:165-178: “Benchmarks for Cystic Fibrosis carrier screening: A European consensus document.”

2 Castellani et al in the Journal of Cystic Fibrosis 7 (2008) 179-196: "Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice"
The answer is edited by: Prof Stuart Elborn