NANA

Question

Dear all,
My son is 11years old.CF del F 508/525del T. (on exon 4). What is the prognose for this combination of genas? Chloride in sweat is 65.We leave in small country Montenegro on the Balkan and we don't have big medical centar for CF,so your answer will help us a lot...Thank you!

Answer

Dear Sir
Sweat chloride concentrations of 65 indicate cystic fibrosis however is
not useful in making a prognosis. F508del is a so-called class II
mutation that means it results in defective processing and maturation of
the CFTR protein that is located in the cell membrane and functions as
an ion channel. Whilst 525delT (on exon 4) causes a frame shift, that
means that the genetic change results in a defective synthesis of the
CFTR protein, so-called class I mutation. As both mutations are considered to be CF causing one expects that the patient shows the
typical clinical picture of CF with impairment of the pancreatic
function and lung disease. In screening the Cystic Fibrosis Mutation
Data Base (www.genet.sickkids.on.ca)
there is one case described with this mutation together with another
CF-causing mutation where the patient showed pancreatic insufficiency
and lung disease. However it has to be stated that many factors may
determine the clinical course of a given patient, either genetic factors
linked to the CF genotype and also modifier genes or environmental
factors. Here it becomes important to stick to the prescribed therapy
and physiotherapy in order to influence the course of the lung disease
positively.The value of genotype for presuming clinical course is
extremely limited as evidenced by very different evolutions that can be
observed among siblings carrying the same mutations. Therefore the
prognosis for this combination of mutations is not known and it is
important to note that making a prognosis based only on genotype is very
difficult. People with the same two copies of the mutated CFTR gene may
experience very different symptoms and therefore prognosis.

I apologise I cannot be any more specific than this
Regards and best wishes
Stuart Elborn

31.03.2011