Mutations F508del and Q220X

Question

Hello,
Our son was diagnosed at birth following a meconium ileus that caused occlusion ...
I would like to have information about delta mutations F508del and Q220X.
Thank you.

Answer

Hello,

Meconium ileus is actually an intestinal blockage occurring in the early days of life in about 15% of children with CF and pancreatic insufficiency. It allows the diagnosis of CF because it is it’s almost exclusive cause.

The F508del mutation is the most frequent mutation of the cystic fibrosis gene (CFTR gene). It is found in France in about 75% of patients and in duplicate (F508del / F508del) in just over 40%. This is a class II mutation that encodes the synthesis of a mutated CFTR protein which is recognized as abnormal by the cell, is destroyed and cannot migrate to the cell membrane to function as a chloride channel.

The mutation Q220X is a class I mutation that causes premature termination of CFTR synthesis hence the name of “stop mutation”. This mutation is rare: the international CFTR2 database, which gathers information from nearly 90,000 patients worldwide, lists 46 patients with this combination F508del / Q220X. The clinical data are comparable to those of nearly 60,000 patients with 2 class I, II or III mutations and correspond to a classical form of CF. For these 46 F508del / Q220X patients, the average age is 19 years, the average chlorine level in sweat is 104 mEq / L, the proportion of patients with pancreatic insufficiency requiring pancreatic enzymes is 100%, the percentage of patients infected with Pseudomonas aeruginosa is 52%. These values are quite comparable to those found in the other group: 19 years also, 100 mEq/L sweat, 92% pancreatic insufficient and 58% colonized by Pseudomonas aeruginosa.

However, these statistic data have to be interpreted with caution, since the evolution of each patient is specific and depends on many environmental factors and factors linked to genes known as modifiers other than those linked to the CFTR gene. In addition, the effectiveness of treatments is continually improving.

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

17.03.2017