Mutations F508del & I507del

Question

Hello,
We are the proud parents of a beautiful boy with the mutations F508 and I507. We would like to have more information on both mutations together.
Our son’s disease looks more digestive than respiratory, although he already had two pseudomonas colonizations (halted by an oral cure and an intravenous cure).
What about Kalydeco® or another product on both mutations?
Thank you in advance

Answer

Hello,

I507del mutation and F508del mutation are both class II mutations. It thus results in the synthesis of an abnormal CFTR protein, largely destroyed in the body of the cell so that only a small part reaches the membrane to act as a channel for the passage of chloride.
In the CFTR2, the largest international database of CF gene mutations, the I507del is, to date, found among 629 patients while the F508del is found in more than 65,000 patients. This database lists about less than 400 patients combining both F508del and I507del mutations and a bit more than 33,000 F508del homozygous patients (ie carriers of the F508del in duplicate).

Chloride levels in the sweat and the percentage of pancreatic insufficient patients are identical in these two populations (sweat Chloride: 100 mmol/L; 98% pancreatic insufficient). For cons, the values of FEV1%, reflecting the degree of respiratory disease is highly variable between patients in the two populations. The degree of respiratory disease depends on many factors, on one hand of genetic factors (type of CFTR mutation but other so-called modifier genes), on the other hand, environmental factors. The type of genotype does not predict the respiratory evolution in a given individual.

Ivacaftor (KALYDECO) is only indicated in patients with Class 3 mutations (including G551D) or Class 4 (R117H). This molecule has not demonstrated evidence of efficacy in patients carry other mutations, including mutations class 2. Ivacaftor and lumacaftor association has demonstrated efficacy in homozygous F508del patients.
If to date, these molecules called modulators of CFTR gene, have proved to be effective for the carriers of certain mutations, they nevertheless marked a decisive turning point in the treatment of cystic fibrosis: other molecules are in development and, no doubt, progress will concern patients with other mutations even if the delays are difficult to predict.

Hoping to have answered your question.
Wishing you a Happy New Year

Gilles RAULT, MD, Roscoff CF Center

27.02.2016