R117H 7T/7T Heterozygous

Question

Hello - My 2-week old daughter is heterozygous R117H 7T/7T. What are her risks of having CF? IRT is low, and sweat test is coming next week. Thank you.

Answer

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.

One mutation (R117H-7T) has been detected, we will come to the meaning of it later. If your daughter only has this one mutation it means she will be a healthy carrier of one CF-mutation and will not suffer from CF.
In the very rare case that there is 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. 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 it is that symptoms occur. Therefore, R117H-7T may result in a mild form of CF, male infertility or no disease at all [1].

In the French screening program, where newborns are systematically screened for CF, many children with mutations R117H-7T/F508del (this second one is a classical CF-mutation) with no CF symptoms were found. Lung problems at young age in patients with delF508 and R117H/7T are very rare. A very recent French report (Jan 2012) shows that R117H/7T in combination with a CF mutation only causes in 0.03% of the cases real CF disease (and in adults only 0.06%).
If you are planning to get genetic counseling, you will get even more detailed information on this topic.


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


1 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"

11.11.2013