ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2012
Functional analysis of synonymous substitutions predicted to affect splicing of the CFTR gene.
Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Case Report: Pulmonary arterial hypertension in children caused by a new mutation in theFrontiers in pediatrics · 2025Article
- A Suite of Foundation Models Captures the Contextual Interplay Between Codons.bioRxiv : the preprint server for biology · 2024Article
- Principles and Practical Considerations for the Analysis of Disease-Associated Alternative Splicing Events Using the Gateway Cloning-Based Minigene Vectors pDESTsplice and pSpliceExpress.International journal of molecular sciences · 2021Review
- Evaluation of both exonic and intronic variants for effects on RNA splicing allows for accurate assessment of the effectiveness of precision therapies.PLoS genetics · 2020Article
- Synonymous variants associated with Alzheimer disease in multiplex families.Neurology. Genetics · 2020Article
- Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells.Nucleic acids research · 2020Article
- CAGI experiments: Modeling sequence variant impact on gene splicing using predictions from computational tools.Human mutation · 2019Article
- regSNPs-splicing: a tool for prioritizing synonymous single-nucleotide substitution.Human genetics · 2017Article
- Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements.Nucleic acids research · 2016Article
- The functional relevance of somatic synonymous mutations in melanoma and other cancers.Pigment cell & melanoma research · 2015Review
- A rigorous approach for selection of optimal variant sets for carrier screening with demonstration of clinical utility.Molecular genetics & genomic medicine · 2015Article
- Experimental assessment of splicing variants using expression minigenes and comparison with in silico predictions.Human mutation · 2014Article
- Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.Nature genetics · 2013Article
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Authors and funding
5 authors.
Funding
Abstract
backgroundCystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 1800 CFTR mutations have been reported, and about 12% of mutations are believed to impair pre-mRNA splicing. Given that several synthetic, non-splice-junction synonymous substitutions have been reported to alter splicing in CFTR, we predicted that naturally occurring synonymous substitutions may be erroneously classified as functionally neutral.
methodsComputational tools were used to predict the effect of synonymous substitutions on CFTR pre-mRNA splicing. The functional consequences of selected substitutions were evaluated using a minigene splicing assay.
resultsTwo synonymous mutations were shown to have a dramatic effect on CFTR pre-mRNA splicing, and consequently could alter protein integrity and phenotypic outcome.
conclusionsTraditional methods of mutation analysis overlook splicing defects that occur at internal positions in coding exons, especially synonymous substitutions. We show that bioinformatics tools and minigene splicing assays are a potent combination to prioritize and identify mutations that cause aberrant CFTR pre-mRNA splicing.
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