User login

Enter your username and password here in order to log in on the website:
Login

Forgot your password?

Please note: While some information will still be current in a year, other information may already be out of date in three months time. If you are in any doubt, please feel free to ask.

Explanations about mutations

Question
Hello
My son, born in mid-November 2014, was diagnosed via Gutrie test perforemd at birth. On the eve of his first month we learned about his illness, and performed a sweat test giving 103mmol / L.
Everything is new and I do not fully understand the mutation he has got.
Indicated two mutations G542X / C3140-26A>G.
Can you tell me to which classes these changes belong and what we know (prediction of pancreatic sufficiency eg) about them?
Thank you very much
Answer
Hello,
The diagnosis of cystic fibrosis (CF) for your son was raised by a positive test and confirmed by both a positive sweat test (> 60 mmol / L chloride in the sweat) and the identification of two CF “causing mutations ".
The G542X mutation is the second most frequent mutation after the main mutation F508delF. It is present in 1803 of more than 40,000 patients registered in CFTR2 international database. This is a class 1 mutation ie causing premature termination of synthesis of the CFTR protein which is destroyed as its synthesis is stopped and cannot migrate to the cell membrane where it cannot acts its role of chloride ion channel. This mutation causes exocrine pancreatic insufficiency when combined with another mutation causing exocrine pancreatic insufficiency.
This is not the case with the mutation 3272-26A> G which is much rarer, present in 186 patients of the CFTR2 database. It causes the synthesis of a mutated protein called c.3140-26A>G which nevertheless retains some functional capacity such that half of the patients who are carriers have no exocrine pancreatic insufficiency (they are called pancreatic sufficient).
This is statistical data that mussn’t draw conclusions for a given individual. The course of the disease depends on many factors, some genetic and innate, others environmental and acquired so that the course of the disease is unique for each individual patient and cannot be stated. This shows the importance of regular monitoring by the multidisciplinary team of a qualified CF Center, including performing at least every 2 years a test (measurement of fecal elastase) to assess the quality of exocrine pancreatic secretion. Pancreatic sufficiency may indeed evolve over time to a failure requiring prescription of pancreatic enzymes.
Hop this answer can help.
With best wishes for a happy New Year. Sincerely.
Gilles RAULT, MD, Roscoff CF Center
13.03.2015