Carrier of a rare mutation

Question

Hello,

Following a family tragedy (the death of my nephew at one month of life because of a rare and serious cystic fibrosis. My sister and her spouse are carriers of a rare gene...). For myself I conducted genetic tests. It turns out that I'm carrying, like my elder sister, a CF gene (which is not part of the classic 80% mutations of the test used in our country).

My husband did the test: he is not carrying a classic mutation either.
We already have a son who is well but what about the next pregnancy? Is there anything we can do to ensure that this kind of tragedy does not happen (in case my spouse would be carrying a rare mutation like my brother in law)?
I was told of further ultrasounds ...
Is it possible to make a complete genome study ?

Answer

Hello,
So you are a carrier of a CFTR gene mutation. If your spouse is also carrying a mutation of this gene, the probability for your couple to give birth to a CF child will, with each pregnancy, be 1 in 4.

Research for your spouse of the most common mutations with the screening kit was in line with national recommendations. Given the possibility that he is a carrier of a rare mutation not included in the kit, this negative result actually leaves a residual risk of 1 in 1000 for your couple give birth to a CF child.

A few specialized laboratories of molecular genetics can now carry out a screening of a larger number of mutations in the CFTR gene. Depending on the number and frequency of additional mutations detected the residual risk may fall between 1 in 3000 and 1 in 7000. These laboratories that can go beyond the national recommendations are few: among them, the three reference French centers for molecular genetics of cystic fibrosis CHU Brest, Cochin Paris, Montpellier.

Regarding the use of further explorations in pregnancy, it would require a prior discussion with specialized teams of medical and molecular CF genetics: Possibility to take a sample of amniotic fluid for dosage of digestive enzyme TIR-PAP? Contribution of ante-natal ultrasounds? If they suspected an affected fetus, they could move towards an extensive search of a mutation in the CFTR gene.

Hope this answer can help.
Best wishes
Gilles RAULT, MD, Roscoff CF Center

05.08.2015