L558S

Question

Hello,
Could you give me some information about this mutation? Is it frequent worldwide? Do the homozygotes have a particular phenotype?
Thank you

Answer

Hello,
CFTR mutations, leading to cystic fibrosis (CF), are numerous and have variable consequences on CFTR protein, and, thus, on disease severity. Over 2000 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 L558S mutation.
As I didn’t know the L558S mutation, I looked at the information available on the CFTR2 website (link: http: // www.cftr2.org /), and questioned a geneticist. It’s a rare mutation, as only 15 patients carrying the L558S are reported in the CFTR2 database. On this site, no further information is currently available, this mutation being still under evaluation. According to the geneticist who I have contacted, 4 patients in France carry this mutation, associated with another CFTR mutation, more frequent.
It is actually recognized that, when combined with another severe CFTR mutation, it usually causes a "classical" form of cystic fibrosis (with a clinical profile comparable to that of patients homozygous for the F508del for example).
This information need to be cautiously considered as the number of reported patients is very low, and as there may exist an important variability in the disease expression from a patient to another. Furthermore, besides CFTR mutations, several parameters can influence the patients’ symptoms evolution; such as the regular follow-up by a specialized team, early treatment of the 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 complexes CFTR mutations. I hope to have answered your questions and do please fill free to reply if you do have other ones.
Best regards
Harriet Corvol

17.12.2014