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Diagnosis CBAVD and PID

Question
Dear expert team,
due to the diagnosis azoospermia of my husband we have been sent to genetic counselling. Suspected diagnosis: translocation.
Result of the molecular genetic investigation of my husband: for the intron 8, the allele combination 55/7T has been found. Therefore, the suspicion of a CBAVD (= Congenital bilateral absence of the vas deferens) caused by CFTR mutation could have been confirmed with the investigations we had (test procedure: INNO-LiPA CFTR17+Tn Update und INNO-LiPA CTFR 19; in my case: no mutation in the CFTR gene could be detected (chromosome Region 7q31.2)).
Interpretation of the result: future children from our partnership have a remaining risk of 0.125% to suffer from a mild form of CF.
Otherwise we have a normal chromosomal result (he: 46XY, me:46,XX). So far, so good. Now our center for reproductive medicine urgently recommended us to have a PID (preimplantation diagnostics) done before the transfer of the ovocyte/embryo. We are insecure, for does the above mentioned result (apart from the rest risk of 0.125%) bears an increased risk for carrying also genetic mutations for illnesses like Huntington's chorea, ß-thalassämia, cystic fibrosis, adrenoleucodystrophia (Addison-Schilder-syndrome), sickle-cell anemia, hemophilia A + B, retinitis pigmentosa, spinale muscle atrophy, Wiskott-Aldrich-syndrome, 21-ß-hydroxylase-deficiency, morbus Charcot Marie Tooth (neural muscular atrophy), myotonic dystrophia (morbus Curschmann-Steinert), Marfan syndrome, Duchenne muscular dystrophy, Becker muscular dystrophy, osteogenesis imperfecta, Torsion dystonia, Lesch-Nyhan-syndrome (hyperurikosis)? How do you judge the foray of our center for reproductive medicine? My husband is 45 years old, and I am 36 years old, we did not have any miscarriages or the like, yet, because no pregnancy so far. Besides that my husband has CBAVD, he does hardly show clinical symptoms of CF. From time to time husky bronchi or constipation. We are looking forward to your opinion and a quick answer. Many thanks!
Answer
Dear questioner,
first of all: I translate the result "55/7T" as CFTR-5T-allele (lays in the intron 8 of the CFTR gene). One does associate an increased risk for CBAVD with that. The other CFTR gene of your husband is a CFTR-7T-allele (and therefore totally healthy, thus harmless).

1. The rest risk: 0.125% may be mathematically correct - should however be more precise: here it deals exclusively with the risk to suffer from the illness of CF due to a CFTR-genetic variant (the CF gene is called CFTR).

2. The CFTR genetic test has NOTHING to do with other hereditary diseases [Huntington's chorea, ß-thalassämia, cystic fibrosis, adrenoleucodystrophia (Addison-Schilder-syndrome), sickle-cell anemia, hemophilia A + B, retinitis pigmentosa, spinale muscle atrophy, Wiskott-Aldrich-syndrome, 21-ß-hydroxylase-deficiency, morbus Charcot Marie Tooth (neural muscular atrophy), myotonic dystrophia (morbus Curschmann-Steinert), Marfan syndrome, Duchenne muscular dystrophy, Becker muscular dystrophy, osteogenesis imperfecta, Torsion dystonia, Lesch-Nyhan-syndrome (hyperurikosis)]. These illnesses have their origin in defects of other genes - not of the CFTR.

3. The proposal of your center for reproductive medicine to have a PID done seems very offensive to me, in case the following is true: in the frame of the diagnostics due to the wish to have children you and your husband have been human genetically investigated and nothing pathological has been found except the CFTR-5T-allele of your husband. This however, I cannot conclude without doubt from your letter: the classification of the result after genotyping of CFTR to illnesses like Huntington's chorea should not happen after a sensible human genetic counselling! We have more than 20.000 genes, the specialist for human genetics must be able to tell you unambiguously, which of those he has been tested, which not and for what diseases these genes are responsible. Please ask there again, if except for the CFTR-5T-allele anything else has been suspicious in the diagnostics.

4. I would like to add a comment about azoospermia and CFTR mutations: in the frame of an infertility treatment mostly CFTR mutations are tested for, in case an azoospermia is underlying. However: azoospermia has several causes: known genetic factors are e.g. the so-called "azoospermia factors", short AZF, that are encoded on the Y-chromosome. Furhtermore, there are different types of azoospermia, e.g. an obstructive azoospermia (with that, in contrast to CBAVD, the ducts are "only" clogged, however anatomically still present). Specialists for this differential diagnosis are andrologists at specialized centers. The following two statements are true for patients with azoospermia and genetic analysis:
Firstly: in patients with azoospermia, mutations in the CFTR gene or in the AZF locus are found more frequently than in healthy people.
Secondly: in many patients with azoospermia no genetic causes for the illness can be found - it is speculated that environmental influences play an important role. Known examples are dye stuff in the clothes, pesticides in the food chain, additives in the overall plastic materials...to cut a long story short: an endless list of chemicals, that we cannot avoid in our industrial society. (source: Statement of the European Society of human genetics, European Journal of Human Genetics (2006) 14, 588–645)
In summary: in case the here by you presented information is complete, I cannot derive a risk for a severe hereditary disease for your planned child. However I do not want to associate myself with the 0.125% rest risk: the CFTR-5T-allele of the father can of course be inherited to the planned child - however or not. The probability is therefore 50% for this, yes, 50% for this, no. It is your decision, if you judge this as a severe risk for the way of life of your child - undoubtfully there is an increased risk with an inherited 5T-allele to have to get help from a center for reproductive medicine oneself later on. You can only make the decision, if you want to have a PID done because of this, in cooperation with the specialist for reproductive medicine (this diagnostic procedure is invasive and bears unfortunately also risks for the unborn life).
With best wishes for both of you - I hope that your wish to have children will be fullfilled soon;

Frauke Stanke
25.03.2014