ArticleJCI insight2019
A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion.Nature communications · 2022Trial
- A novel deep intronic COL5A1 variant in an Ehlers-Danlos syndrome family: functional characterization by minigene assay.Scientific reports · 2026Article
- Training Together, Diagnosing Better: Federated Learning for Collagen VI-Related Dystrophies.ArXiv · 2025Article
- Detection of differentially expressed genes in bantam chickens providing insights into chicken dwarfism.BMC genomic data · 2025Article
- Characterization of severe COL6-related dystrophy due to the recurrent variant COL6A1 c.930+189C>T.Brain : a journal of neurology · 2025Article
- Splice-modulating antisense oligonucleotides targeting a pathogenic intronic variant in adult polyglucosan body disease correct mis-splicing and restore enzyme activity in patient cells.Nucleic acids research · 2025Article
- Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Collablots: Quantification of Collagen VI Levels and Its Structural Disorganisation in Cell Cultures From Patients With Collagen VI-Related Dystrophies.Neuropathology and applied neurobiology · 2025Article
- Nanomechanics of cell-derived matrices as a functional read-out in collagen VI-related congenital muscular dystrophies.Journal of the Royal Society, Interface · 2025Article
- Restored Collagen VI Microfilaments Network in the Extracellular Matrix of CRISPR-Edited Ullrich Congenital Muscular Dystrophy Fibroblasts.Biomolecules · 2024Article
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Strategies to improve the design of gapmer antisense oligonucleotide on allele-specific silencing.Molecular therapy. Nucleic acids · 2024Article
- Allele-specific CRISPR-Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.Molecular therapy. Nucleic acids · 2024Article
- Optimized allele-specific silencing of the dominant-negativeMolecular therapy. Nucleic acids · 2024Article
- The recurrent deep intronic pseudoexon-inducing variantmedRxiv : the preprint server for health sciences · 2024Article
- Neonatal X-linked myotubular myopathy with a de novo mutation: A case report and literature review.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Allele-specific CRISPR/Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.bioRxiv : the preprint server for biology · 2024Article
- A humanized knock-inbioRxiv : the preprint server for biology · 2024Article
- Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis.Briefings in bioinformatics · 2023Review
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Authors and funding
35 authors at 13 institutions in 8 countries.
Funding
Abstract
The clinical application of advanced next-generation sequencing technologies is increasingly uncovering novel classes of mutations that may serve as potential targets for precision medicine therapeutics. Here, we show that a deep intronic splice defect in the COL6A1 gene, originally discovered by applying muscle RNA sequencing in patients with clinical findings of collagen VI-related dystrophy (COL6-RD), inserts an in-frame pseudoexon into COL6A1 mRNA, encodes a mutant collagen α1(VI) protein that exerts a dominant-negative effect on collagen VI matrix assembly, and provides a unique opportunity for splice-correction approaches aimed at restoring normal gene expression. Using splice-modulating antisense oligomers, we efficiently skipped the pseudoexon in patient-derived fibroblast cultures and restored a wild-type matrix. Similarly, we used CRISPR/Cas9 to precisely delete an intronic sequence containing the pseudoexon and efficiently abolish its inclusion while preserving wild-type splicing. Considering that this splice defect is emerging as one of the single most frequent mutations in COL6-RD, the design of specific and effective splice-correction therapies offers a promising path for clinical translation.
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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.