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Published on: February 11, 2017
The relative frequency of CFTR mutation classes in European patients with cystic fibrosis
K De Boeck1, A Zolin2, H Cuppens3
1Department of Pediatrics, University Hospitals of Leuven, Belgium.
Abstract:
More than 1900 different mutations in the CFTR gene have been reported. These are grouped into classes according to their effect on the synthesis and/or function of the CFTR protein. CFTR repair therapies that are mutation or mutation class specific are under development. To progress efficiently in the clinical phase of drug development, knowledge of the relative frequency of CFTR mutation classes in different populations is useful. Therefore, we describe the mutation class spectrum in 25,394 subjects with CF from 23 European countries. In 18/23 countries, 80% or more of the patients had at least one class II mutation, explained by F508del being by far the most frequent mutation. Overall 16.4% of European patients had at least one class I mutation but this varied from 3 countries with more than 30% to 4 countries with less than 10% of subjects. Overall only respectively 3.9, 3.3 and 3.0% of European subjects had at least one mutation of classes III, IV and V with again great variability: 14% of Irish patients had at least one class III mutation, 7% of Portuguese patients had at least one class IV mutation, and in 6 countries more than 5% of patients had at least one class V mutation.
Insights
This study analyzed CFTR mutation classes in over 25,000 European cystic fibrosis patients. Class II mutations are most common, but class I, III, IV, and V frequencies vary significantly across countries, impacting targeted therapy development.
Area of Science:
- Genetics
- Molecular Biology
- Medical Science
Background:
- Over 1900 mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene are known.
- CFTR mutations are classified by their impact on protein synthesis and function.
- Targeted CFTR repair therapies are under development, requiring knowledge of mutation class frequencies.
Purpose of the Study:
- To determine the mutation class spectrum in European cystic fibrosis (CF) patients.
- To provide data useful for the clinical development of mutation-specific CFTR therapies.
Main Methods:
- Analysis of mutation class data from 25,394 CF patients across 23 European countries.
- Categorization of mutations based on their effect on CFTR protein synthesis and function.
Main Results:
- Class II mutations, primarily F508del, were present in 80% or more of patients in 18/23 countries.
- 16.4% of European patients had at least one class I mutation, with significant country-to-country variation (30% to <10%).
- Class III, IV, and V mutations were less common overall (3.9%, 3.3%, 3.0% respectively), but showed notable regional prevalence (e.g., 14% class III in Ireland).
Conclusions:
- The distribution of CFTR mutation classes varies considerably across European populations.
- Understanding this spectrum is crucial for optimizing the clinical development and deployment of targeted CFTR therapies.
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