Heterozygous mutation F508del with deletion exon 17a and b

Question

Dear ladies and gentlemen,

is there any research about the above mentioned mutations?
Could VX770 be also helpful here?
What does the above mentioned mutation mean? We have been told that our daughter (1 year) will be with the utmost probability compound heterozygous.
Many thanks for your answer in advance

Answer

Hello,

the term compound-heterozyougs means, that your daughter has inherited the mutation F508del from one parent and the deletion of the exons 17a and b from the other parent. In case only your daughter has been tested, one can not talk about that she is compoud heterozygous with a 100% security (but only "with the utmost probability"), because in principle both mutations can be on one parental gene and from the other parent another mutation has been inherited, that has not already been found. The confirmation of the mutations in both parents is not only important in the context of genetic questions (e.g. family planning, testing of carriers in uncles and aunts of the patient) but also in the future with regard to new therapeutic options.
While at the moment several drugs for the mutation class specific therapy in patients with the mutation F508del are tested promisingly in clinical studies, this development is much less progressed in case of rarer mutations as the deletion of exons 17a and b.

VX-770 as a so-called potentiator, can only be effective in those mutations, where a CFTR-chloride channel is present at the cell surface. In case of the mutation F508del this is only very limited the case, so that here also other drugs are used like VX-809, which should help as a "corrector" to bring the wrong folded CFTR-protein to the cell surface. It is investigated at the moment in clinical studies, in how far the combination of a corrector with a potentiator is well-tolerated and effective.

For the deletion of the exons 17a and b is at the moment not clear, to which class of mutations these mutations belong to. The choice of the "mutation class specific drug" does however depend to a great extent on the mutation class.
But, however, even if in the future there would not be a specific therapy for the deletion of the exons 17a and b, in spite of this a specific therapy could make sense concerning the in your daughter also underlying mutation F508del. In theory it is sufficient, in case of a compound-heterozygous patients, to get rid of the cellular effects of one of the two mutations. In case of success, there would then be a Heterozygousity, like in the parents of the CF patient, that means, without sings of illness.

One may reckon that in the near future drugs for the therapy of CF-patients with the mutation F508del will be licensed. Via the CF-center of your daughter you will certainly be informed about that. Here it will also be a point, from which age on the patients are allowed to be treated with the drug (probably there will be an age-restricted licensing).

Yours sincerely,
Prof. Stuhrmann-Spangenberg

10.10.2011