Genetic variation in CFTR and modifier loci may modulate cystic fibrosis disease severity
Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disease in Caucasians caused by variants in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel expressed in epithelial cells throughout the body . To date, over 2,000 variants in the CFTR gene have been identified world-wide. The international CF genetics research community has contributed these data to the CFTR2 database (http://www.cftr2.org), which provides information on different CFTR variants and their disease liability by a phenotype-driven approach .
Authors: Williams M, Jacobson KA Abstract The recent cloning of a number of distinct receptors belonging to the P2-purinoceptor superfamily has provided conclusive evidence for a pivotal role for ATP and other nucleotides as effector molecules involved in cell-to-cell communication and the modulation of many basic aspects of tissue function. ATP itself is being clinically evaluated as a cytotoxic agent for the treatment of cancer and as an adjunct to inhalation anaesthetic use. The pyrimidine nucleotide, UTP, is in clinical trials for the treatment of cystic fibrosis. The stable ATP bioisostere, ARL 67085, is being...
Publication date: Available online 12 December 2019Source: Journal of Molecular Graphics and ModellingAuthor(s): Sabahuddin Ahmad, Sudha Bhagwati, Sushil Kumar, Dibyendu Banerjee, Mohammad Imran SiddiqiAbstractCathepsin S (CatS) is one of the cysteinyl cathepsins widely studied for its clinical significance and found to be a promising therapeutic target for several diseases; to name a few is arthritis, allergic inflammation, cancer, diabetes, obesity, and cystic fibrosis. Elevated CatS level is a contributing factor for related disorders, and therefore among different strategies to regulate the activity of CatS, one is to ...
ConclusionCF patients with pulmonary exacerbations have worse SNOT ‐22 and CFQ‐R 14+ scores than CF patients at their baseline health. This finding suggests a temporal relationship between sinonasal and pulmonary quality of life, and that worsening of both is associated with reduced pulmonary function.
This study provides insights on polymicrobial interactions that may influence the progression of CF-associated pulmonary infections.
In this study, we used site-directed spin-labeling electron paramagnetic resonance spectroscopy to examine the interaction of ExoU with soluble analogs of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). We found that dioctanoyl PI(4,5)P2 binds to and induces conformational changes in a C-terminal four-helix bundle (4HB) domain of ExoU implicated previously in membrane binding. Other soluble phosphoinositides also interacted with the 4HB but less effectively. Molecular modeling and ligand docking studies indicated the potential for numerous hydrogen bond interactions within and between interhelical loops of the 4HB and...
Nutritional status, assessed by weight or body mass index (BMI), has long been recognized as an important predictor of lung function (FEV1) and mortality in patients with cystic fibrosis (CF) [1,2]. Patients are often encouraged to consume a diet high in calories to offset the negative energy expenditure created by malabsorption, increased work of breathing, inflammation, and pulmonary exacerbations. Improved medical and nutritional therapies and the recent introduction of CFTR modulators have contributed to increased incidence of overnutrition in patients with CF.
CONCLUSION: The analysis of the presence of 5T polymporphism in CBAVD patients may add information when predicting the outcome of assisted reproductive techniques. PMID: 31823853 [PubMed - in process]
Conclusions: S. aureus SAgs belonging to the EGC are highly prevalent in CF clinical isolates. The greater prevalence in these SAgs in CF airway specimens compared to skin isolates suggests that these toxins confer selective advantage in the CF airway.
ConclusionThe eastern and the northern provinces have the highest prevalence of CF, with the c.2988+1G>A (3120+1G>A) and c.1418delG (p.Gly473GlufsX54) variants showing the highest distribution in the Saudi CF population, which may reflect the effect of consanguinity within the same tribe. Proper family screening and counseling should be emphasized.
ConclusionsThe present protocol based on the entire CFTR gene together with informative SNPs outside and inside the gene can be applied to diagnose all CF mutations at preimplantation stage.