ArticleScientific reports2020
The Fuchs corneal dystrophy-associated CTG repeat expansion in the TCF4 gene affects transcription from its alternative promoters.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Systematic review of SLC4A11, ZEB1, LOXHD1, and AGBL1 variants in the development of Fuchs' endothelial corneal dystrophy.Frontiers in medicine · 2023Pooled it
- Tcf4 CTG Repeat Expansion Induces RNA Toxicity and MBNL-Associated Splicing Dysregulation in a Mouse Model of Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- Transcription factor 4 and Fuchs' endothelial corneal dystrophy (FECD) association: Perspectives for novel targeted therapeutics.Eye (London, England) · 2025Article
- Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.Molecular diagnosis & therapy · 2025Article
- A genome-wide approach for the discovery of novel repeat expansion disorders in the Undiagnosed Diseases Network cohort.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Comprehensive analysis of splicing variants in corneal endothelial cells of patients with Fuchs endothelial corneal dystrophy.Scientific reports · 2025Article
- The TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2025Article
- Dysregulation of the TCF4 Isoform in Corneal Endothelial Cells of Patients With Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2024Article
- Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy.Scientific reports · 2024Article
- Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.PLoS genetics · 2024Article
- Expression of alternative transcription factor 4 mRNAs and protein isoforms in the developing and adult rodent and human tissues.Frontiers in molecular neuroscience · 2022Article
- Time- and Stimulus-Dependent Characteristics of Innate Immune Cells in Organ-Cultured Human Corneal Tissue.Journal of innate immunity · 2022Article
- Lower Fractions ofGenes · 2021Article
- Molecular mechanisms underlying nucleotide repeat expansion disorders.Nature reviews. Molecular cell biology · 2021Review
- Genetic mutations and molecular mechanisms of Fuchs endothelial corneal dystrophy.Eye and vision (London, England) · 2021Review
- Article
- Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy.PloS one · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The CTG trinucleotide repeat (TNR) expansion in Transcription factor 4 (TCF4) intron 3 is the main cause of Fuchs' endothelial corneal dystrophy (FECD) and may confer an increased risk of developing bipolar disorder (BD). Usage of alternative 5' exons for transcribing the human TCF4 gene results in numerous TCF4 transcripts which encode for at least 18 N-terminally different protein isoforms that vary in their function and transactivation capability. Here we studied the TCF4 region containing the CTG TNR and characterized the transcription initiation sites of the nearby downstream 5' exons 4a, 4b and 4c. We demonstrate that these exons are linked to alternative promoters and show that the CTG TNR expansion decreases the activity of the nearby downstream TCF4 promoters in primary cultured neurons. We confirm this finding using two RNA sequencing (RNA-seq) datasets of corneal endothelium from FECD patients with expanded CTG TNR in the TCF4 gene. Furthermore, we report an increase in the expression of various other TCF4 transcripts in FECD, possibly indicating a compensatory mechanism. We conclude that the CTG TNR affects TCF4 expression in a transcript-specific manner both in neurons and in the cornea.
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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.