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Rare mutation - R709X
- Question
- Hello,
When my CFTR gene was sequenced the nonsense-mutation R709X (c.2125C>T) was detected. Furthermore, the molecular genetic findings of the Medical School Hannover (MHH, Germany) states that this mutation in combination with the 3272-26A>G mutation is most likely "compound heterozygous".
What does "compound heterozygous" means in this context? Which mutation specific therapy forms would come into question?
Many thanks,
B.
- Answer
- Hello,
most likely "compound-heterozygous" means that you most likely inherited one of the mentioned mutations from your father and one from your mother. If your parents would do a test this assumption could be confirmed if each of your parents was heterozygous for one of both mutations at a time. In this case you would be "compound-heterozygous" (and would therefore have cystic fibrosis) for both mutations and each of your parents would be heterozygous for only one of both mutations. Almost half of all CF patients are compound-heterozygous (and thus have inherited two different mutations in the CFTR gene) and the rest of the CF patients is homozygous (the exact same mutation was inherited from both parents in this case).
In very rare cases it also happens that there are two different mutations in a CFTR gene. Therefore, in theory it is also possible that you received both detected mutations from one of your parents and from the other parent a mutation that is still unknown. Such a constellation would have consequences for the testing of healthy family members of yours with regard to heterozygosity since heterozygosity can only be excluded if it is assured that you are really compound-heterozygous.
Particularly, in consideration of a possible mutation specific therapy in your case it would be necessary to have the compound-heterozygosity confirmed by having your parents tested. The mutation R709X is a class-1-mutation where a so called single base substitution led to an early stop codon. This is also called nonsense-mutation. For this mutation the drug ataluren (PTC 124) could be effective. You should talk with your CF center about this. For the other mutation 3272-26A>G there is currently no mutation specific therapy available.
Best regards,
Prof. Stuhrmann-Spangenberg - 07.05.2012
