Gene Mutation

Question

I have been diagnosed with deltaF508 and 2789+5G>A gene mutation. What is my future prognosis and is it a mild or a serious CF form?

Answer

Hello,
before we will make a comment on the special mutation you mention, it is important to stress that the genotype of a certain patient (his underlying CFTR-mutations) is not suitable for making an individual prognosis, as the individual prognosis of a CF patient does not only depend on the underlying mutations but also on other genetic and environmental factors, especially on the initiated therapy and its adherence to it. However, even if making an individual prognosis is impossible, the genotype and the mechanism how it influences the production of CFTR-protein, gives a hint, if one can expect rather a "classical" or a "milder" form of the disease.
Out of the two CFTR-mutations the patient carries, the "milder" one determinates the picture; this is in your case the 2789+5G>A gene mutation. This mutation is a so-called "splicing mutation"; the splicing process is an important step when reading out the gene leads to the production of a special protein. This spicing mutation can still result in a fraction of correctly spliced products, and as the proportion of correctly vs. aberantly spliced product can vary from patient to patient, some patients can have a relatively mild phenotype, yet with variable disease expression, from minimal lung disease, pancreatic sufficiency and male fertility to a relative severe disease in all the involved organs. At the moment, an extensive international research focusing on this type of mutation is well under way. However, the results haven´t been announced yet.
But as mentioned above, your prognosis depends on many factors, so that a good CF therapy and supervision in a specialized center is of greatest importance.
Dr. J. Brázová and Dr. D. d'Alquen

13.12.2011