Classification of the illness possible? What to do?

Question

Hello,
many thanks for your help in advance!
Please tell me, how I have to react to the following conditions in order to find out, if I suffer from CF and what I can do in order to impede the development of further clinical symptoms:
Age: 36, male, in the frame of a genetic investigation at a center for reproductive medicine, genetic defects have been detected (before hypozoospermia in the history, diagnostics for infertility in case of CFTR-related disease).
Bronchial Asthma, allergic rhinoconjunctivitis, chronic sinusitis, delta F508 heterozygous, >>> exon 1-27:genotype: c.(1521_1523del) (;) (3080T>C), furthermore protein level: p.(Phe508del) (;) (lle1027Thr), actually normal lung function, exclusion of exocrine insufficiency, ultrasound of the upper abdomen normal, vitamin D deficiency, sweat test 1 in the control area with chloride 42, sodium 67 mmol/l, sweat test 2 positive with chloride 61, sodium 81 mmol/l.
Please tell me first of all, if the 2nd defect, that has been found at the complete gene sequencing, is known and what the consequences could be.
Thank you!

Answer

Dear questioner,
on the basis of the genetic investigation, also the complete sequencing, the diagnosis can unfortunately not be made unambiguously.
First of all, CF is a so-called recessive disaese, that only breaks out, if both chromosomes (thus the maternal and also the paternal) carry a defect. That is most probably not the case in your situation:
1. mutation F508del - a clear CF mutation, however:
2. result: the variant Ile1027Thr is more frequently found on the same chromosome as the mutation F508 del (this information is given in a case report from Suareza et al, Grand Rounds Vol 12 pages 36–39).
That means in translation: the human genetic specialist would still have to find out after sequencing, if also in your case the variant Ile1027Thr is on the same chromosome as the mutation F508del (then the result for your second chromosome is namely "unknown/no mutation found").
However also after further human genetic works an unambiguous diagnosis stays out, as the variant Ile1027Thr cannot be estimated in its effect (in case it is independent of F508del) and a full sequencing unfortunately does not allow an exclusive diagnostics.
In order to get a reliable diagnosis, please turn to a specialized center for measurment of the basis defect of CF, as the affected protein in case of CF is a chloride channel and one can measure, if it is functioning. Such specialists can at the moment be found in Germany in the follwoing cities: Bochum (Dr. Ballmann, Heidelberg (Dr. Mall), Berlin (Dr. Derichs) and Hannover (Dr. Tümmler).
With best wishes,
Frauke Stanke

28.02.2014

28.2.14
In order to influence positively the course of this probable "CFTR-related disorder" or "mild form of CF" (more clarity will bring assumingly the measurement of the basis defect as mentioned above), it will be of utmost importance to be followed up regularly in a specialized CF-Center in order to control lung function, bacterial colonization of airways and others. By this, early therapeutical measures can be initiated and so prevent further damage.
D. d'Alquen