E1104X Mutation

Question

Hello,
My eldest son, 16 and a half years old, has cystic fibrosis with G542X / E1104X mutations.
My mutation, E1104X, is native of the Maghreb (kabylie for my part but by searching on the net, I understand that there are children being homozygous for E1104X in Tunisia).
This mutation is therefore not so rare, I would like to know if you could tell me which class it belongs to please?
I cannot find this information on the net.
Does a person with two class 1 mutations necessarily has a worse prognosis?
It seems to me but I do not exactly remember that the pediatrician of my son told me suddenly that he had 2 mutations of class 1 (G542X being in class 1).
Thank you.
Cordially.

Answer

Hello,

The two mutations G542X and E1104X are class I mutations. These are so-called "Stop" mutations because the replacement of a sequence of the mutated gene with a Stop codon causes a premature interruption of the synthesis of the protein. This truncated protein, recognized as abnormal, is destroyed in the nucleus of the cell and cannot reach the cell membrane where it should normally migrate to perform its chloride channel function.
The G542X mutation is relatively frequent: in the international CFTR2 database, which collects information from nearly 100,000 individuals with cystic fibrosis and is found in 3474 of them. The E1104X mutation is indeed rare: it is found only in 17 patients who may be of Maghreb origin for some of them but this database does not give information on the ethnic origin or geographical location of patients.
Patients with two CFTR class I, II or III mutations statistically have a classical form of cystic fibrosis with exocrine pancreatic insufficiency and a positive sweat test. However, these statistical data does not allow to predict the evolution of the disease which is specific to each patient because it depends on many other environmental factors (lifestyle, pollution ...) and genetics linked to genes other than the gene Cystic fibrosis but which can modify its expression, which are called "modifying genes" and are currently being researched.

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

24.02.2017