Compund heterozygous for F508del and R117h

Ερώτηση

Dear ladies and gentlemen,
the above mentioned mutations have been found in my case, when I (32 years old) had already been pregnant via IVF (in-vitro fertilization). I did the investigation, as these mutations had also been found in my brother when he was investiagted in a clinic for reproduction as he wished to have children. These mutations are in trans.
During my pregnancy, I visitied a CF center. All investigations were not pathological, a sweat test had not already been done. However, a colonization with Staph. aureus had been found.
My question: Is this a combination of mutations in which sooner or later classical symptoms occur or is this rather an atypical form?
Best regards,

Απάντηση

*this answer had been posted nearly word for word in March 2017 for 2 questions in ECORN-CF*
Dear questioner,
R117H is a CFTR variant, that is difficult to classify: an overview article with 31 CF-genetists form 13 countries (Castellani et al, Journal of Cystic Fibrosis 2008) classifies R117H as a mutation from category A "CF-causing" or (!) as a mutation from category B "cause of a CFTR-caused disorder / atypical CF". One could also say: the mutation cannot be classified (F508 del is e.g. always A - CF causing). The difference between CF and atypical CF is the grade of severity of the illness as well as the manifestation: a classical CF has symptoms since early childhood in many organs - in case of CF the lung, the gut and digestion, reproductive organs and many things more are involved. In case of an atypical CF, symptoms occurr only in adulthood and not all organs are involved. Therefore, the sweat test can show values in the upper normal range in case of the combination F508del/R117H, or carriers of the combination F508del/R117H can be healthy except impaired fertility. As you do not describe the typical symptoms of CF, I assume, that you suffer from an atypcial form of the CFTR-caused disorder - this however cannot be concluded from the description of the human genetist, however from your description. From this we can conclude that we cannot predict the further course of the CFTR-related disorder (therefore the occurrence of symptoms) from the genetic results - how should this be possible if the mutation R117H cannot be classified properly in the category A or B. The recommendation fot the international website CFTR2 for the combination F508del/R117H is therefore, to present regularly at your physician - even if there are no other symptoms yet except an impaired fertility.

Dr. Frauke Stanke

12.06.2017