ArticleAmerican journal of respiratory cell and molecular biology2017
The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations.
Article in American journal of respiratory cell and molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Low-Dose Ketone Monoester Administration in Adults with Cystic Fibrosis: A Pilot and Feasibility Study.Nutrients · 2024Trial
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Epithelial NaComprehensive Physiology · 2024Review
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Preclinical evaluation of the epithelial sodium channel inhibitor AZD5634 and implications on human translation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Downregulation of epithelial sodium channel (ENaC) activity in cystic fibrosis cells by epigenetic targeting.Cellular and molecular life sciences : CMLS · 2022Article
- Association of cystic fibrosis transmembrane conductance regulator with epithelial sodium channel subunits carrying Liddle's syndrome mutations.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- DNA Methylation Patterns Correlate with the Expression ofInternational journal of molecular sciences · 2021Article
- First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.ERJ open research · 2021Article
- ENaC inhibition in cystic fibrosis: potential role in the new era of CFTR modulator therapies.The European respiratory journal · 2020Review
- An innovative phase II trial to establish proof of efficacy and optimal dose of a new inhaled epithelial sodium channel inhibitor BI 1265162 in adults and adolescents with cystic fibrosis: BALANCE-CFERJ open research · 2020Article
- Preclinical evaluation of the epithelial sodium channel inhibitor BI 1265162 for treatment of cystic fibrosis.ERJ open research · 2020Article
- Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies.Pharmaceutics · 2020Review
- High-mobility group box-1 increases epithelial sodium channel activity and inflammation via the receptor for advanced glycation end products.American journal of physiology. Cell physiology · 2020Article
- Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico.Pediatric pulmonology · 2020Article
- Oxidized Glutathione Increases Delta-Subunit Expressing Epithelial Sodium Channel Activity ineMedical research · 2020Article
- Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases 2017. An Official American Thoracic Society Workshop Report.American journal of respiratory cell and molecular biology · 2019Article
- The ex vivo human lung: research value for translational science.JCI insight · 2019Review
- New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature.Current opinion in nephrology and hypertension · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 11 institutions in 5 countries.
Funding
Abstract
Cystic fibrosis (CF) remains the most lethal genetic disease in the Caucasian population. However, there is great variability in clinical phenotypes and survival times, even among patients harboring the same genotype. We identified five patients with CF and a homozygous F508del mutation in the CFTR gene who were in their fifth or sixth decade of life and had shown minimal changes in lung function over a longitudinal period of more than 20 years. Because of the rarity of this long-term nonprogressive phenotype, we hypothesized these individuals may carry rare genetic variants in modifier genes that ameliorate disease severity. Individuals at the extremes of survival time and lung-function trajectory underwent whole-exome sequencing, and the sequencing data were filtered to include rare missense, stopgain, indel, and splicing variants present with a mean allele frequency of <0.2% in general population databases. Epithelial sodium channel (ENaC) mutants were generated via site-directed mutagenesis and expressed for Xenopus oocyte assays. Four of the five individuals carried extremely rare or never reported variants in the SCNN1D and SCNN1B genes of the ENaC. Separately, an independently enriched rare variant in SCNN1D was identified in the Exome Variant Server database associated with a milder pulmonary disease phenotype. Functional analysis using Xenopus oocytes revealed that two of the three variants in δ-ENaC encoded by SCNN1D exhibited hypomorphic channel activity. Our data suggest a potential role for δ-ENaC in controlling sodium reabsorption in the airways, and advance the plausibility of ENaC as a therapeutic target in CF.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.