Genetic, environmental, and stochastic factors contribute to phenotype variation of diseases in childhood. Disease variability in patients with Cystic Fibrosis (CF) bearing the same combination of mutations emphasizes the role of genetic background and environment, which appears to be the rule rather than the exception. Cystic fibrosis (CF), a single-gene-recessive disorder, is an ideal model for the identification and characterization of factors that cause disease variation. As a matter of fact its monogenic etiology allow a better and schematic study of the possible gene mutations that characterize the disease variability and severity. The dysfunctional protein Cystic Fibrosis transmembrane regulator (CFTR) in CF patients conducts chloride across the apical membranes of polarized epithelia. Loss of CFTR function affects the transport of chloride, sodium, and water across epithelial tissues, leading to inadequate hydration of mucous secretions in CF patients. Patients with CF manifest disease in the lungs, pancreas, intestine, liver, male reproductive tract, and sweat gland. The amount of CFTR required by each organ involved in the disease to remain phenotypically “normal” varies, and, similarly, the extent to which each organ contributes to the CF phenotypes varies in each individual. Moreover the complex genetic expression is further modified by both environmental factors and other genetic influences such as those coming from modifier genes, that also contribute to the disease severity. Thus, these influences increase the number of phenotypic expressions of the same disease. The aim of this review is to analyse the multiple phenotypic aspects of Cystic Fibrosis related to the genotypic mutations that determine this high variability of the same disease and to describe our personal clinical experience.
Cystic Fibrosis a prism with thousand sides: a genotype-phenotype analysis.
VITALITI G;
2012
Abstract
Genetic, environmental, and stochastic factors contribute to phenotype variation of diseases in childhood. Disease variability in patients with Cystic Fibrosis (CF) bearing the same combination of mutations emphasizes the role of genetic background and environment, which appears to be the rule rather than the exception. Cystic fibrosis (CF), a single-gene-recessive disorder, is an ideal model for the identification and characterization of factors that cause disease variation. As a matter of fact its monogenic etiology allow a better and schematic study of the possible gene mutations that characterize the disease variability and severity. The dysfunctional protein Cystic Fibrosis transmembrane regulator (CFTR) in CF patients conducts chloride across the apical membranes of polarized epithelia. Loss of CFTR function affects the transport of chloride, sodium, and water across epithelial tissues, leading to inadequate hydration of mucous secretions in CF patients. Patients with CF manifest disease in the lungs, pancreas, intestine, liver, male reproductive tract, and sweat gland. The amount of CFTR required by each organ involved in the disease to remain phenotypically “normal” varies, and, similarly, the extent to which each organ contributes to the CF phenotypes varies in each individual. Moreover the complex genetic expression is further modified by both environmental factors and other genetic influences such as those coming from modifier genes, that also contribute to the disease severity. Thus, these influences increase the number of phenotypic expressions of the same disease. The aim of this review is to analyse the multiple phenotypic aspects of Cystic Fibrosis related to the genotypic mutations that determine this high variability of the same disease and to describe our personal clinical experience.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
