ArticleBrain : a journal of neurology2019
MSH3 modifies somatic instability and disease severity in Huntington's and myotonic dystrophy type 1.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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106 citing papers in PubMed, 162 citations in OpenAlex.
- Stage-dependent tau-PET signatures in Huntington's disease revealed by [¹⁸F]PI-2620.European journal of nuclear medicine and molecular imaging · 2026Article
- Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.bioRxiv : the preprint server for biology · 2026Article
- Conference proceedings from the Western Canadian Neuromuscular Conference (WCNMC) - September 27-29, 2024, Calgary, Canada.Journal of neuromuscular diseases · 2026Article
- Reconciling the effects of PMS2 in different repeat expansion disease models supports a common expansion mechanism.PNAS nexus · 2026Article
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.Clinical epigenetics · 2026Article
- Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion.NAR molecular medicine · 2026Article
- Expanding repeats, expanding impact: Somatic instability in myotonic dystrophy type 1.Journal of neuromuscular diseases · 2026Review
- In Vivo PET Imaging of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism.American journal of human genetics · 2026Article
- Observational
- Disrupted Transcriptional Networks in Mammalian Cells Stably Over-Expressing Pathogenic Atrophin-1.Journal of neuroscience research · 2025Article
- DNA extrusion size determines pathway choice during CAG repeat expansion.Nucleic acids research · 2025Article
- Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.Nature reviews. Neurology · 2025Review
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- Disrupted Transcriptional Networks by Mutant Atrophin-1 in a Cell Culture Model of Dentatorubral-Pallidoluysian Atrophy.bioRxiv : the preprint server for biology · 2025Article
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- CellPHIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington's Disease, Including Genetic Modifiers of Neuronal Development and Morphology.bioRxiv : the preprint server for biology · 2025Article
- Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.Molecular systems biology · 2025Article
- Article
46 more citing papers are in PubMed but not listed here.
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13 authors at 6 institutions in 4 countries.
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Abstract
The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CAG·CTG repeat expansion disorders Huntington's disease and myotonic dystrophy type 1. A recent Huntington's disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington's disease. Using Illumina sequencing in Huntington's disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG·CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington's disease and myotonic dystrophy type 1, and slower progression (P = 3.86 × 10-7) in Huntington's disease. RNA-Seq of whole blood in the Huntington's disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington's disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington's disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases.
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