CF mutations

Vraag

The mother carries the mutation G542X in heterozygote status and the father the nucleotic change c.949G>C (p.Val317Leu) of the CFTR gene. The fetus, after an amniocentesis carries the G542X mutation from the mother and the p.Val317Leu mutation from the father. How severe will the CF be?

Antwoord

Dear friend,
The CFTR gene is a large one with many mutations (more than 2000 till now). In order to assess the clinical significance of the mutations, as it will be expressed in the dysfunction of the CFTR protein, a large international database (CFTR2) has been established. During the last registry (8/12/2017), based on data from 89059 CF patients, the following record exists:

312 mutations cause CF
36 mutations have variable clinical manifestations
13 mutations do not cause CF
13 mutations are of unknown clinical significance.

The G542X is one of the most common CF mutations in the Greek population, with a rate of 3.9%.
The p.Val317Leu mutation is not included in the CFTR2 database, and there are no international published data about its clinical significance. In the case you describe the fetus carries a mutation that causes a typical form of CF and another mutation, of unknown clinical significance. It is not known if this combination will cause a typical, or a mild form of the disease.
My personal opinion, which is based on the fact that the p.Val317Leu mutation is not found in over 170000 chromosomes of CF patients, is that it is probably a simple mutation that does not cause a typical form of CF.
Yours friendly,
Dr. Stavros Doudounakis

25.05.2018