Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Respiratory System, CFTR mutations, Cystic fibrosis, Genotype, Prevalence, CFTR mutation classes, Allele frequency, MORTALITY, SURVIVAL, GENOTYPE, COHORT, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, DNA, DNA Mutational Analysis, Europe, Female, Gene Frequency, Humans, Male, Mutation, Retrospective Studies, 1103 Clinical Sciences, 3202 Clinical sciences

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.