Diagnosis F508del and R1162X

Question

Hello,
my 11-months old son has been diagnosed to suffer from CF and F508del and R1162X have been detected.
However, during the talk it became unfortunately not clear to me what kind of form it deals with here.
Is that a rare combination?
Can you make a recommendation for a CF center in North Rine-Westphalia [Germany]?

Answer

Hello,
today, there are already 2000 mutations described in the CFTR gene, that is responsible for cystic fibrosis (CF). These mutations can be devided into 6 classes, according to their influence on the synthesis or the function of the CFTR protein (chloride-ion channel). Class I-III mutations result in a defective synthesis, processing, maturation and regulation of the CFTR protein with a functional loss of the ion channel. Class IV-V mutations result in an impaired conductance, reduced function/synthesis and an increased degradation of the CFTR protein, however still with a remaining expression and function of the ion channel, which leads to a milder course of the illness compared to Class I-III mutations. If a patient has on his two CFTR genes mutations from different classes, the less severe mutation determines the function of the protein and therefore part of the clincal picture of CF.
Both mutations of your son belong to Class I (R1162X) and II (508del). This constellation is not rare. In the CFTR2 database there is the clinical data summerized of 341 patients with the genotype F508del/R1162X and can be seen there (www.cftr2.org/).

However it has to be taken into account, that the clinical course and especially the degree of the lung disease is not determined by the mutations of the patient alone but that many other genetic (modifier genes, individual genetic background) and environmental factors play a role. Therefore the grade of severity and the course of the illness cannot be foreseen precisely, as they can even vary markedly between patients with the exact same mutations. Therefore it is very important, that the patient is seen regularly in a certified CF center and follows his individual treatment program.
I hope to have helped you with my remarks and stay with my best regards,
Prof. Dr. Sabina Gallati

26.10.2015