Gene mutation of delta F 508/2789+5G-A, Work in a pigsty

Question

Dear expert team,
I am 37 years old, male and I am suffering of a very mild variant of CF. I have the mutations F 508 and 2789+5G-A. My brother died as a child because of CF. Can you give me some information about my mutations? Is it possible that my health condition will worsen sometime?
Now I have another question: in the last time I have been visiting a friend frequently and we were in his pigsty, where the strong smell caused light pain in my lungs. Is it advisable for me to avoid stables in general?
Many thanks in advance,

Yours sincerely

Answer

Hello,
to the first question: To answer this question, I consider it helpful to describe briefly the terms "genotype" and "phenotype": The "genotyp" describes individual changes in the human genome. So far, over 1400 different mutations in the so called “CF-gene” (on chromosom 7), which codes for a chloride channel (so-called CFTR) have been identified. Over 80% of CF-patients in Germany are carriers of the mutation deltaF508, which has been identified in your case, too. The mutation deltaF508 (so-called point-mutation) causes an incorrect protein structure of the CFTR chloride channel, resulting in reduced biological function. Compared to the deltaF508 mutation, the second mutation identified in your case (2789+5G-A) is rare and is found in less than 1% of the CF-patients in Germany. This so-called "splice mutation" causes an error in reading of the CF-gene in the nucleus of the cell (transcription) followed by a decreased synthesis of CFTR chloride channels. While the "genotype" can be determined only by molecular-biological analysis, the "phenotype" describes the clinically apparent disease. Possible connections between specific "genotype" and "phenotype" have been examined in numerous CF-studies, however, for most cases a specific genotype could not be linked to a specific grade of disease severity; this is particularly evident in respect to CF-lung disease. It is postulated that so far unidentified changes in genes other than the CF-gene (so-called modifier genes) could result in different clinical pictures in individuals with the same laboratory confirmed genetic CF-defect.
Interestingly, a recently published study from France examines the phenotype of 34 CF patients with the identical combination of mutations identified in your case (so-called compound heterozygous deltaF508/2789+5G-A). The results demonstrate a clearly milder progress of illness when compared to the typical progress of CF-disease (I. Dugueperoux, M. de Braekeleer. Eur Respir J 2005; 25:468 473). I think those results are encouraging for you, even if your state of health (as asked in your question) might potentially worsen one day.
For further information about "genotyp/phenotyp" issues with CF I recommend a recent overview article, which can be download free of charge from the homepage of the German CF-Foundation (www.muko.info/1122.0.html) (language: German).

To your second question: The typical stinging smell in the pigsty results mainly from the production of ammonia and hydrogen sulfide. Both materials can irritate the airways and provoke inflammation even to lungs of healthy individuals. In particular animals that are so-called “kept appropriate to the need of the species”, i.e. with addition of straw and sawdust, high air pollutions with bacteria, mold fungi and their dismantling products were measured. Therefore, specialists for occupational medicine strongly recommend to further increased preventive measures (in particular protection of the respiratory system) for employees in agriculture.
In this context I would advise patients suffering from chronic lung disease (like CF-patients) to avoid occupational (and also spare time) activities in a pigsty.
Yours sincerely
TO Hirche

26.11.2007