Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients.

Cystic Fibrosis Newborn Screening in Portugal: PAP Value in Populations with Stringent Rules for Genetic Studies

“…Despite large clinical heterogeneity, respiratory tract symptoms dominate CF pathology, with early impaired pulmonary function and lung disease being the major cause of morbidity and mortality in CF [5]. Adding to the broad phenotypic spectrum, a large genotypic variety is also observed (particularly in some regions, like Southern Europe), with genotype-phenotype correlations difficult to establish due to the involvement of multiple genetic modifiers and environmental factors [6,7].…”

Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT Versus IRT/PAP/IRT

“…Our experience using the IRT/IRT strategy over the last 8 years is that although we are able to detect CF newborns on time [12] and hardly ever detect carrier or cystic fibrosis screen positive with an inconclusive diagnosis (CFSPID) cases, our low PPV (15.1%), false positive rate (0.13%), and the number of second DBS specimens that must be requested are unacceptable. At the moment, genetic studies cannot be done in our region without written informed consent, so we were not able to evaluate introducing a CFTR mutation panel into the protocol in addition to measuring PAP concentration [13].…”

“…Many detection programs have been developed in Europe since the end of the 1980s, though there is marked variation in the designs of the NBS protocol [11]. However, given the considerable geographical, ethnic, and economic variations, a single approach would not be appropriate [12,13].All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT) in DBS specimens [14]. IRT is a nonspecific marker that increases in most CF patients.…”

“…Many detection programs have been developed in Europe since the end of the 1980s, though there is marked variation in the designs of the NBS protocol [11]. However, given the considerable geographical, ethnic, and economic variations, a single approach would not be appropriate [12,13].…”

Adeno-Associated Virus (AAV) gene therapy for cystic fibrosis: current barriers and recent developments

“…It is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel involved in the generation and maintenance of a tiny layer of fluid on the surface of mucosal membranes of the airways, gastrointestinal tract, epididymis, liver, and pancreas 5 . In these organs, failure to produce the layer of fluid causes sticky mucus secretions, leading to chronic lung infection and inflammation, GI obstruction, male infertility, liver disease, and failure to digest food as a result of the loss of pancreatic duct function 67 . In the sweat ducts, failure to absorb chloride from the ducts leads to elevated concentrations of NaCl in the sweat, even at rest 8 .…”