title: The Impact on Genetic Testing of Mutational Patterns of CFTR Gene in Different Clinical Macrocategories of Cystic Fibrosis.
abstract: More than 2000 sequence variations of the cystic fibrosis transmembrane conductance regulator gene are known. The marked genetic heterogeneity, poor functional characterization of the vast majority of sequence variations, and an uncertain genotype-phenotype relationship complicate the definition of mutational search strategies. We studied the effect of the marked genetic heterogeneity detected in a case series comprising 610 patients of cystic fibrosis (CF), grouped in different clinical macrocategories, on the operative characteristics of the genetic test designed to fully characterize CF patients. The detection rate in each clinical macrocategory and at each mutational step was found to be influenced by genetic heterogeneity. The definition of a single mutational panel that is suitable for all clinical macrocategories proved impossible. Only for classic CF with pancreas insufficiency did a reduced number of mutations yield a detection rate of diagnostic value. All other clinical macrocategories required an extensive genetic search. The search for specific mutational classes appears to be useful only in specific CF clinical forms. A flowchart defining a mutational search that may be adopted for different CF clinical forms, optimized in respect to those already available, is proposed. The findings also have consequences for carrier screening strategies.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy; Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy; Policlinico Umberto I Hospital, Rome, Italy. Electronic address: marco.lucarelli@uniroma1.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucarelli
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Sabina M
authors.initials: SM
authors.lastname: Bruno
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy; Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pierandrei
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Ferraguti
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy; Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Testino
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Gessica
authors.initials: G
authors.lastname: Truglio
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy; Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Strom
authors.affiliation: Policlinico Umberto I Hospital, Rome, Italy; Department of Pediatrics, Sapienza University of Rome, Rome, Italy; Cystic Fibrosis Reference Center of Lazio Region, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Quattrucci
mesh_terms: D000483:Alleles; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D057188:Workflow
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator