ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 84 citations in OpenAlex.
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- Tissue-level heterogeneity in FECD: Descemet's membrane phenotypes and association with TCF4 CTG18.1 expansionThe Journal of pathology · 2026Article
- Deep learning-driven prediction of on-target activity, off-target risk, and repair outcomes in CRISPR/Cas9: current landscape and multi-scale perspectives.Journal of translational medicine · 2026Review
- Targeted long-read sequencing for high-resolution repeat profiling in myotonic dystrophy type 1.Experimental & molecular medicine · 2026Article
- MASTR-seq enables multiplexed analysis of short tandem repeats with sequencing.Cell reports methods · 2026Article
- Article
- Longitudinal Study ofMedical sciences (Basel, Switzerland) · 2026Article
- Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.Molecular diagnosis & therapy · 2025Article
- Hybridization capture long-read sequencing and de novo assembly of homologous haplotypes: a comprehensive hemophilia test.Blood advances · 2025Article
- Long-read sequencing reveals extensivebioRxiv : the preprint server for biology · 2025Article
- CRISPR-Cas-Based Diagnostics in Biomedicine: Principles, Applications, and Future Trajectories.Biosensors · 2025Review
- Repeat Expansion and Somatic Instability in TCF4 in Patients With Fuchs Endothelial Corneal Dystrophy Identified by Small Pool PCR.Investigative ophthalmology & visual science · 2025Article
- Generation of a Mouse Model of Fuchs Endothelial Corneal Dystrophy by Knock-in of CTG Trinucleotide Repeat Expansion in the TCF4 Gene.Investigative ophthalmology & visual science · 2025Article
- Transgene Mapping in Animals: What to Choose?International journal of molecular sciences · 2025Review
- Heterozygous Tcf4 Deficiency Mitigates Fuchs Endothelial Corneal Dystrophy Progression in a Mouse Model.Investigative ophthalmology & visual science · 2025Article
- Cas9-based enrichment for targeted long-read metabarcoding.Royal Society open science · 2025Article
- Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.Nucleic acids research · 2025Review
- Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.Molecular neurodegeneration · 2024Article
- Leveraging the power of long reads for targeted sequencing.Genome research · 2024Review
- Age-dependent somatic expansion of the ATXN3 CAG repeat in the blood and buccal swab DNA of individuals with spinocerebellar ataxia type 3/Machado-Joseph disease.Human genetics · 2024Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeTo demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1).
methodsWe applied an amplification-free method, utilizing the CRISPR/Cas9 system, in combination with PacBio single-molecule real-time (SMRT) long-read sequencing, to study CTG18.1. FECD patient samples displaying a diverse range of CTG18.1 allele lengths and zygosity status (n = 11) were analyzed. A robust data analysis pipeline was developed to effectively filter, align, and interrogate CTG18.1-specific reads. All results were compared with conventional polymerase chain reaction (PCR)-based fragment analysis.
resultsCRISPR-guided SMRT sequencing of CTG18.1 provided accurate genotyping information for all samples and phasing was possible for 18/22 alleles sequenced. Repeat length instability was observed for all expanded (≥50 repeats) phased CTG18.1 alleles analyzed. Furthermore, higher levels of repeat instability were associated with increased CTG18.1 allele length (mode length ≥91 repeats) indicating that expanded alleles behave dynamically.
conclusionCRISPR-guided SMRT sequencing of CTG18.1 has revealed novel insights into CTG18.1 length instability. Furthermore, this study provides a framework to improve the molecular diagnostic accuracy for CTG18.1-mediated FECD, which we anticipate will become increasingly important as gene-directed therapies are developed for this common age-related and sight threatening disease.
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