Phenotype associated to Genotype F508del / 3849+10 kbCT

Question

Hello I am 5 months pregnant. My husband has got the F508del gene, and I'm carrying the 3849 + 10 kb CT.
With 1/4 chance to transmit CF, I would like to know the clinical features.
Best Regards

Answer

Hello,
The F508del mutation, the most common mutations in the CFTR gene (cystic fibrosis gene), is present in more than 2/3 of CF patients. As a class II mutation, it results in synthesis of a mutated CFTR protein which is destroyed because recognized as abnormal and cannot ensure its functioning as a chloride channel in cell membrane. It is known as a "CF-causing" mutation say it results in CF when combined with another CF-causing mutation.
The mutation 3849 + 10kb C>T is much less common, present in 59 patients CFTR France database and in 500 of the nearly 40,000 patients registered in the CFTR2 international database. As a class V mutation, it causes the synthesis of a functional CFTR protein but in insufficient quantities.

Even though considered "CF-causing" the 3849 + 10kb C>T mutation results however often in moderate forms.

286 patients with genotype F508del / 3849 + 10kbC>T are registered in the CFTR2 base. The average value of their sweat test is 66 mmol / l and 33% of them are pancreatic insufficient. For comparison, more than 30,000 patients in the CFTR2 base having at least one F508del associated with another CF-causing mutation have a sweat test averaging 99 mmol / l and 90% of them are pancreatic insufficient.
It should be reminded that the single genotype does not predict the clinical course of a given patient because it depends on many factors, genetic but not related to CFTR gene or environmental.

Hope this answer can help.
Best wishes
Gilles RAULT, MD, Roscoff CF Center

07.06.2015