mutation

Question

My 9-months-old daughter is homozygous for the c.489+1G>T mutation. Can you tell me more about her form of cystic fibrosis; how much is it widespread and severe?
Thank you in advance for your answer.

Answer

Hello,
The mutation c.489 +1G>T is the new name of the mutation known as 621+1G>T.
This mutation is present in 793 out of 39,696 (2 %) patients in the CFTR2 international data base of the Johns Hopkins Hospital, Baltimore, Maryland, USA. Although much less common than the most frequent mutation (F508del) it is one of the 23 most frequent and well identified " CF causing mutations" ie mutations that cause cystic fibrosis when combined with another "CF causing" mutation or in the homozygous state.
The CFTR2 data base accounts 25,696 patients combining two of the main 23 CF causing mutations. Though the number of homozygous patients for the mutation c.489+1G> T as your daughter is not indicated, the results in terms of sweat test (average >100 mmol/L), the frequency of pancreatic insufficiency (> 93%) or FEV1% are comparable - if either mutation c.489+1G >T is present or not in the genotype combining 2 of the 23 main CF causing mutations.
If you are fluent in English, you can access the site CFTR2 by clicking the following link:
cftr2.org/mutation.php?view=general&mutation_id=15

However, keep in mind that the evolution of the disease is dependent on many genetic and environmental factors. The sole genotype can not allow to predict the evolution of the disease in a given individual.
That shows the importance of personal attention by the multidisciplinary team in a specialized CF center. The physician who follows your daughter will be best placed to provide you with details. You can also apply for a medical genetics consultation: your doctor can give you information about a CF experienced genetic counselor near your home.
Hope that answers your question.
Cordially.
Gilles Rault, MD
Nantes-Roscoff CF Expertise Center

12.05.2014