**1.1. Classes of mutation in cystic fibrosis**

The CFTR protein is a cAMP-regulated chloride channel that resides in the apical membrane of epithelial cells of different organs such as the intestines, lung, pancreas, and sweat glands. However, the main pathologic symptom of cystic fibrosis (CF) is respiratory disease with recurring infections, inflammation, and obstructions that induce progressive lung damage and possible respiratory difficulties [1].

More than 1,900 different CFTR mutations have been reported so far and can be generally categorized into five classes (Table 1). Approximately 40% of CFTR mutations belong to class I. Nonsense mutations cover 10% of CF patients, but in some populations specific nonsense mutations can occur in up to 50% of CF subjects. For example, G542X mutation, the most common CFTR nonsense mutation, has been found in 2% of Caucasian CF patients. The most frequent mutation of class II is the F508del mutation (a deletion of the phenylalanine residue at position 508) found in 75% of CF patients. While for class III, the G551D mutation has been found in approximately 4% of CF patients. Class I-III mutations determine an important defect in CFTR function and cause a severe CF phenotype, while mutations belonging to Classes IV-V permit a residual CFTR protein function and induce a milder CF phenotype. There is general consensus on the fact that in order to ameliorate the CF phenotype, the restoration of at least 5–35% of normal CFTR function is necessary [1-4].


**Table 1.** Principal classes of CF mutations and therapeutic intervention.
