c.4251delA

Question

Hello,
I previously posted a message to know the impact of the 4472delT mutation. Actually I got confused because my son is a carrier of this mutation on the SAMD gene, not on the CFTR gene for that he is c.4251delA homozygous.
Please remove my previous question please. What would the impact of this mutation?

Answer

Hello,
The c.4251delA CFTR gene mutation, according to the new nomenclature (the usual name is 4382delA), is only identified that in 28 of more than 40,000 patients of the CFTR2 database. It is indicated as a CF causing mutation when associated with another CF causing mutation. This is the case of your child who is homozygous for this mutation (as you stated in your previous question).
Regarding all other patients of this database, the clinical outcomes of the 28 CF patients carrying a c.4251delA mutation are statistically:
• comparable with regards to the values of the sweat test and the forced expiratory volume in one second (FEV1)
• but differ with regard to the frequency of pancreatic insufficiency which is only present in fewer than half (40%) of 28 patients carrying the c.4251delA mutation (whereas it is present in 87% of other patients).
Keep in mind those are just statistical data: one cannot draw conclusions for a given individual, because the clinical course depends on many factors, both genetic and environmental, which make the history of each patient unique. This is the justification for a personalized follow-up by the multidisciplinary team of specialized CF Center: do not hesitate to take stock of the situation with them and ask them the questions that concern you.
Moreover, the mutation 4472delT is actually not a CFTR gene mutation but a mutation of the SAMD-9 gene involved in tumoral normophosphatemic familial calcinosis. I am not aware of any interference with a CFTR gene mutation.
Sincerely.
Dr. Gilles Rault CRCM Roscoff

03.12.2014