mutation R533X and R933G

Question

Hello,
I have heterozygous mutations R533X and R933G on each chromosome. To which class of mutations do they belong and what organ diseases do they cause?
Thank you.

Answer

Hello,
The R553X mutation is a class 1 mutation (or mutation associated with a stop codon). By cons, it is impossible to classify R933G until a ​​functional study has been done. According to the French CF registry, sweat tests also indicate values ​​"questionable or negative" for patients with this mutation associated with a classic mutation (class 1 or 2).
I asked a specialist in genetics, who indicates that this mutation is rather associated with milder forms than F508del homozygotes, but still a wide spectrum. Of 5 observations, all with compound heterozygous for a mutation R933G and severe
- 2 adults were infertile, one had discrete lung disease;
- 1 had a pancreatic disease and moderate and late pulmonary disease
- 2 were infants diagnosed through neonatal screening, one had pancreatic insufficiency.
So it seems to be a mutation associated with so-called moderate forms which may include a male infertility, respiratory rather late and rarely gastrointestinal tract.

Soon will be available an online database, called CFTR2 which includes anonymous information about more than 40 000 patients living in Europe or North America.
In general however it has to be stated, that one cannot predict the clinical course only according to the genotype, as the phenotype is influenced besides the genotype by other genetic and environmental factors (e.g. care, adherence to therapy etc.). Therefore analysing the genotype can only give a rough direction and cannot predict the individual course of the disease.
Sincerely,
Dr Sophie Ravilly and Emmanuelle Girodon

23.12.2011