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Semin Respir Crit Care Med 2015; 36(02): 180-193
DOI: 10.1055/s-0035-1547318
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genotypes and Phenotypes in Cystic Fibrosis and Cystic Fibrosis Transmembrane Regulator–Related Disorders

Cristina Bombieri
1   Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
,
Manuela Seia
2   Molecular Genetics Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
,
Carlo Castellani
3   Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
› Author Affiliations
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Publication History

Publication Date:
31 March 2015 (online)

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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.

Keywords

cystic fibrosis - CFTR-related disorders - CFTR mutations - genotype–phenotype correlations - CBAVD - pancreatitis - bronchiectasis - modifier genes
 

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