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Dutch CF Registry 2017 - Demographic data

Mutations in CF 


CF is caused by a genetic mutation in the chloride channel, the CFTR protein. The CFTR protein is essential for a good water-salt balance in the body. If the CFTR protein is not made properly, various organs do not perform as well and also start to malfunction. There are many different genetic disorders of the CFTR gene, and someone is classed as a CF patient if he/she has two copies (one inherited from the father and one from the mother). The most common genetic mutation of CFTR is F508del. 

Figure 1 below shows that more than half of patients with CF (55%) have two F508del mutations (F508del/F508del), 34% have one F508del and another mutation (F508del/other), and the rest of the patients have two other (sometimes unknown) mutations or have not been tested for the type of mutation.


The F508del mutation is the most common, as can be seen in this table, which shows the 15 most common mutations.

There are more than 2000 known genetic mutations of the CFTR gene. These mutations can be classified according to the effect they have. One method is to divide them into five classes:

  • Class 1: no (complete) protein strand is created from the DNA, so that no chloride channel can be folded
  • Class 2: a protein strand is created, but it is not properly folded in 3D into a chloride channel, and therefore broken down again by the cell
  • Class 3: a chloride channel is created, but it hardly opens to let chloride through, and the channel is therefore ineffective
  • Class 4: this class includes the milder CFTR mutations, where the chloride channel works, but less often than in healthy people
  • Class 5: the mutations in this class are also somewhat milder; the chloride channel is created, but not enough and/or it does not remain active for a long time

Figure 2 below shows the class of the mildest mutation (of the two mutations per person). The most common F508del mutation is a class 2 mutation, and that class is the most prevalent: 75% of people have a class 2 mutation as the mildest of the two CFTR mutations.