Mutations L206W and S1251N

Question

Hello, I'm 26 years old and I have no symptoms of cystic fibrosis but these two mutations (discovered after diagnosis of CF in my two children). What do we know about these 2 mutations L206W and S1251N?

Answer

Hello,

According to the International CFTR2 database containing clinical and genetic data from nearly 70,000 CF individuals, S1251N and L206W are "CF causing" mutations, ie they cause cystic fibrosis when associated in the same individual to another "CF causing" mutation.

The L206W mutation is characterized by replacement of the amino acid leucine (L) with the amino acid tryptophan (W) at position 206 of the cystic fibrosis gene, the CFTR gene. It is found in 330 individuals in the database. The average value of the sweat test is to 76mEq/L (against 96 mEq/L for other patients of the database). The exocrine pancreatic insufficiency requiring pancreatic enzyme intake is only found in 20% of patients who are carriers of this mutation (against 85% of the other patients of the database). In fact, the CFTR protein whose synthesis is encoded by the mutated gene retains more often a residual function of the chloride channel. This mutation, identified for the first time in patients from the South of France is also found more frequently in Canadian Quebec.

The S1251N mutation is characterized by replacing the amino acid serine (S) with the amino acid Asparagine (N) in position 1251 of the CFTR gene. It is found in 120 individuals in the CFTR2 database. The average value of the sweat test is 84 mEq/L. 86 of these 120 patients (72%) are pancreatic insufficient. This is a Class III mutation, that does not affect the amount of synthesized CFTR protein or its migration to the cell membrane but which affects the input of chlorine in the channel. Patients with this mutation are eligible for treatment with ivacaftor.

To return to your personal case, it should be noted that the correlations between genetic data (genotype) and clinical course (phenotype) have a statistic value. They provide an indication for the analysis of individual situations but other factors may influence the clinical course ie environmental factors or other genetic factors including modifier genes that can modulate more or less the expression of the CFTR gene.

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

27.02.2016