Requestion on „F508del mutation – other mutations possible?”

Question

My question is related to the question „F508del mutation – other mutations possible?” (http://ecorn-cf.eu/index.php?id=65&L=0&tx_expertadvice_pi1[showitem]=916&tx_expertadvice_pi1[search]=)
from the 14.06.2010, for sure this is some time ago, from that answer I understood that a genetic investigation of the parents seems to be sensible, however I could have understood something wrong. I had understood, that the genetic analysis of my daughter (2.5 years) was not decisive. Do I get it right that if we are not both heterozygous carriers of the mutation it is not imperative that further children inherit the mutation with a probability of 25%? However, both parents must have a defect, even if it is not the same mutation, or, if there is no homozygousity, it can not come to a CF in case of a new pregnancy??
Does the insurance pay by the way for such a test?
Thank you very much and best regards.
V.M.

Answer

Dear Mrs. M.,
Yes, you got it right that a genetic investigation of the parents would be sensible, in order to be able to say securely, that the second mutation of your daughter is also a F508del mutation or however a greater deletion (loss of part of the gene), which do also comprise the location of the F508del-mutation (Exon 10).The reason why this differentiation could not have been done with the performed analyzing methods in your daughter so far , is only for technical reasons and does not question the diagnosis nor has it a meaning for the therapy. Like I explained already in my first answer, the correct identification of both mutations is of importance with regard to your further family planning, as well as for your relatives (siblings, cousins etc.).
In general, a child which is homozygous for the mutation F508del can only hail from a partnership, in which both parents are heterozygous for the mutation F508del. Hereditary factors of human beings are on chromosomes in duplication: one chromonsome is inherited from the father, one from the mother. It comes only to the illness of CF in the child if both genes on the chromosomes (that means the one from the father and the mother) carry the mutation for CF. In case it is the same mutation (e.g. the father as well as the mother is carrier for F508 del mutation), it is called homozygous. If one of the parents is carrier of another mutation, which leads also to CF, and both parents inherit again their mutation to the child, the child suffers also from CF, however with two different underlying mutations.
This is called compound-heterozygous. The parents themselves are clinically healthy in both cases, have only on one chromosome the changed gene, this is a heterozygous carrier state.
Is therefore a child homozygous or compound-heterozygous for a CF mutation, the parents have to be heterozygous each and for any further pregnancy of your partnership there is the risk of 25%, that the child will also suffer from CF, as you have been told by your doctors. For the prognosis, also other genes and environmental factors play a role, so that only based on the genetic result a statement about the individual clinical course cannot be made.
You ask further, if the insurance covers the costs for a genetic analysis of the CF-parents. This is the case in special situations. Please contact your insurance directly to get this information.

I hope to have clarified your answer,
Best regards,
Prof. Sabina Gallati, Dr. H.-G. Posselt und Dr. D. d‘Alquen

11.04.2011