title: Genotypes and phenotypes in cystic fibrosis and cystic fibrosis transmembrane regulator-related disorders.
abstract: Cystic fibrosis (CF) is characterized by remarkable variability in severity, rate of disease progression, and organ involvement. In spite of the considerable amount of data collected on the relationship between genotype and phenotype in CF, this is still a challenging matter of debate. Barriers to the interpretation of this connection are the large number of mutations in the CF transmembrane regulator (CFTR) gene, the difficulties in attributing several of them to a specific mode of dysfunction, and a limited number of the almost 2,000 mutations so far detected, which have been clinically annotated. In addition to that, the heterogeneity of clinical manifestations in individuals with the same CFTR genotypes indicates that disease severity is modulated by other genes and by environmental factors, of which the most relevant is possibly treatment in its aspects of appropriateness, early start in life, and adherence. The phenotype variability extends to conditions, named CFTR-related disorders, which are connected with CFTR dysfunction, but do not satisfy diagnostic criteria for CF. The current level of knowledge does not allow use of the CFTR genotype to predict individual outcome and cannot be used as an indicator of CF prognosis. This might change with the development of treatments targeting specific mutations and possibly capable of changing the natural history of the disease.
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bombieri
authors.affiliation: Molecular Genetics Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Seia
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castellani
mesh_terms: D001987:Bronchiectasis / Q000235:genetics*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D060045:Genes, Modifier; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics*; D010641:Phenotype
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator