ArticleEuropean journal of human genetics : EJHG2014
The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells.
Article in European journal of human genetics : EJHG, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- An accurate prediction model of digenic interaction for estimating pathogenic gene pairs of human diseases.Computational and structural biotechnology journal · 2022Article
- Article
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- Cystic Fibrosis: Systems Biology Analysis from Homozygous p.Phe508del Variant Patients' Samples Reveals Perturbations in Tissue-Specific Pathways.BioMed research international · 2021Article
- The GENDULF algorithm: mining transcriptomics to uncover modifier genes for monogenic diseases.Molecular systems biology · 2020Article
- Constraining classifiers in molecular analysis: invariance and robustness.Journal of the Royal Society, Interface · 2020Article
- The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease.Frontiers in pharmacology · 2020Review
- Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights.Genes · 2019Review
- Recent advances in developing therapeutics for cystic fibrosis.Human molecular genetics · 2018Review
- Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity.Nucleic acids research · 2017Article
- [Interstitial processes of the lungs in childhood].Der Pathologe · 2017Review
- Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.Frontiers in pharmacology · 2017Review
- Deep resequencing ofHuman genome variation · 2016Article
- Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis?Molecular and cellular pediatrics · 2015Article
- Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.PloS one · 2015Article
- The Contribution of the Airway Epithelial Cell to Host Defense.Mediators of inflammation · 2015Review
- Disease-modifying genes and monogenic disorders: experience in cystic fibrosis.The application of clinical genetics · 2014Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The three-base-pair deletion c.1521_1523delCTT (p.Phe508del, F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most frequent disease-causing lesion in cystic fibrosis (CF). The CFTR gene encodes a chloride and bicarbonate channel at the apical membrane of epithelial cells. Altered ion transport of CFTR-expressing epithelia can be used to differentiate manifestations of the so-called CF basic defect. Recently, an 11p13 region has been described as a CF modifier by the North American CF Genetic Modifier Study Consortium. Selecting the epithelial-specific transcription factor EHF (ets homologous factor) as the likely candidate gene on 11p13, we have genotyped two intragenic microsatellites in EHF to replicate the 11p13 finding in the patient cohort of the European CF Twin and Sibling Study. We could observe an association of rare EHF haplotypes among homozygotes for c.1521_1523delCTT in CFTR, which exhibit a CF-untypical manifestation of the CF basic defect such as CFTR-mediated residual chloride secretion and low response to amiloride. We have reviewed transcriptome data obtained from intestinal epithelial samples of homozygotes for c.1521_1523delCTT in CFTR, which were stratified for their EHF genetic background. Transcripts that were upregulated among homozygotes for c.1521_1523delCTT in CFTR, who carry two rare EHF alleles, were enriched for genes that alter protein glycosylation and trafficking, both mechanisms being pivotal for the effective targeting of fully functional p.Phe508del-CFTR to the apical membrane of epithelial cells. We conclude that EHF modifies the CF phenotype by altering capabilities of the epithelial cell to correctly process the folding and trafficking of mutant p.Phe508del-CFTR.
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