F508del+L206W mutations

Question

Hello, we transmitted to our daughter the F508del and L206W mutations. She is one month old today and has already a severe gut disease (very short small intestine after a meconium ileus). The L206W mutation seems rare in France. What grade of severity of lung disease have similar compound heterozygous patients worldwide? Thanks you for your answer (support).

Answer

Hello,
CFTR mutations, leading to cystic fibrosis (CF), are numerous and have variable consequences on the CFTR protein, and, thus, on disease severity. Over 1900 CFTR gene mutations are described actually in the CFTR2 database. Most of these mutations are punctual mutations, and the most frequent ones are missense mutations (42%), such as the L206W mutation.

As I didn’t know the L206W mutation, I looked at the information available on the CFTR2 website (link: http: // www.cftr2.org / mutation.php? View=general*mutation_id=41), and at the last scientific publications reporting information on this mutation when coupled to the F508del. As you highlighted, this is a rare mutation, as the CFTR2 database reports only 134 patients worldwide with at least one copy of L206W, among which 99 are, as your daughter, composite heterozygous L206W/F508del.

When combined with F508del, it usually causes a "classical" form of cystic fibrosis (with a clinical profile comparable to that of patients homozygous for the F508del for example). However, according to the information available on this website, some L206W/F508del patients have no pancreatic insufficiency, and may have a milder respiratory disease, with a lower rate of lung function decline, and with less frequent Pseudomonas aeruginosa respiratory infections.

This information needs to be cautiously considered as the number of patients is very low, and as there exists an important variability in the severity of the disease from one patient to another. Furthermore, besides CFTR mutations, several parameters influence the patients’ symptoms evolution; as the regular follow-up by a specialized team, early treatment of infections and a good nutrition status. All these parameters could favorably influence the prognosis.

You may ask all these questions to your daughter’s CF doctor, as he/she might be able to give you more appropriate information. You could also ask to meet a geneticist or a geneticist counselor who will be able to explain these rather complexe CFTR mutations.

Finally, a support word… if your daughter had a severe digestive disease at birth (meconium ileus), it does not foresee a greater severity of the disease afterwards. Important progresses have been made in the CF care, and are still pursuing.

I hope to have answered your questions and please feel free to reply if you do have other ones.

Best regards

Harriet Corvol

27.02.2014