Mutation T338I

Question

Hello
My son aged 22 months was diagnosed three weeks after the postnatal test.
He has the G542X and T338I mutations. The geneticist we encountered explained that this was a rather mild form of CF. Our son has five airway clearance sessions per day, salt and vitamins ADEK, no pancreatic enzymes. He goes very well, never had bronchitis. I find the treatment heavy for a child who doesn’t look sick. I quite understand the protocol but eventhough I know that we don’t have enough elapsed time and that each case is different are you able to tell me a bit more about his mutations, if other patients in the world have the same mutations as my son’s and what is the progression of the disease on them.
Thank you in advance for your answer

Answer

Hello,
The G542X is a mutation of the CFTR gene (the gene involved in cystic fibrosis). It’s found in France in 2.4 % of patients and is the second most common mutation behind the delta F 508. It is called a "stop" mutation because it stops the synthesis of the corresponding protein and causes CFTR cellular dysfunction as a result of a defective chloride channel responsible for the CF symptoms.
The T338I change in the CFTR gene have been found in France in 5 cases:
• 2 cases of screened newborns whose diagnosis of CF was confirmed by a positive sweat test: we do not have information on their clinical course yet;
• 3 cases of congenital absence of the vas deferens (the ducts of sperm) without proved CF. This anomaly is almost constant and the cause of infertility in men with CF. It can however occur in isolation in non-CF people with a negative sweat test and no CF causing mutations.
The low number of cases and the lack of clinical experience does not allow so far to qualify it as a CF causing mutation rather than a simple variation of the CFTR gene not causing CF.
The fact that your son is going well, he had no bronchitis, he is unlikely to have pancreatic exocrine insufficiency (he has no treatment of pancreatic enzymes) suggests that he has either an mild type of CF (if the sweat test is positive: you didn’t specify your son’s sweat test result) or a CFTR related disorder, say a symptom associated with a mutation of the CFTR gene without further evidence of CF.
Monitoring these borderline situations is recommended even if the frequency of visits and treatment including chest physiotherapy can be adapted. A research protocol called “DPAM” has also been established in France for this purpose: should you need further information, feel free to contact your CF Center.
Hope that answers your question.
Gilles RAULT, MD, CF Center Roscoff, France

23.12.2013