Delta F508 x G542X mutation

Question

Dear expert team,

My two-month-old daughter has the mutations mentioned above; class 2 and class 1, respectively, i.e. very serious mutations.

Do you know about any progressions of the disease with this combination? What should we expect? Can you recommend any drugs?

My daughter is gaining weight quite well at the moment, and she does not seem to show any symptoms.

We will test her for bacteria and lung function next week.

Results apart from the gene test as of now:
1) IRT 131,5 ng/mL
2) pancreatic elastase: [translator’s note: some information seems to be missing in the original question]

Answer

Hello,

There is a big, worldwide study from the early 90s by "The Cystic Fibrosis Genotype - Phenotype Consortium" (New England Journal of Medicine, 1993, 329:1308-1313) about the effects of specific CFTR mutations on the clinical development of CF. By comparing 399 F508del homozygous patients with 148 patients who (like your daughter) are "compound heterozygous" for F508del and G542X, it was possible to show that the patients from both groups do not differ in any of the parameters examined (such as age of diagnosis, lung function, pancreatic function, etc.). In other words: your daughter’s genotype (i.e. the mutations present) is a typical CF genotype, exactly like homozygosity for F508del.

It is impossible to make exact predictions about the progression in CF, since it may vary significantly even in patients with the exact same genotype. At any rate, your daughter should present at a CF centre on a regular basis, where the doctors could then also talk to you about the necessary precautionary and therapeutic measures (which depend on the patient’s individual health status).

One exception in drug therapy, however, now is the so-called mutation (class)-specific therapy. Particularly for certain class-1 mutations, there are quite promising approaches with ataluren, a drug that can be used with certain stop mutations, and perhaps also with G542X. For the F508del mutation, there are studies concerning a specific drug therapy as well. The latter are not as advanced as ataluren (PTC-124).

At this point, the question from which age mutation (class)-specific drugs will be approved for the treatment of CF cannot be answered unequivocally. Here, I would again like to point you to your daughter’s CF clinic where you will be able to obtain further information as it becomes available (the development is rather quick, and the doctors at the CF clinic are following it constantly).

Kind regards
Prof. Stuhrmann-Spangenberg

07.05.2012