ArticleBrain : a journal of neurology2021
The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis.Molecular neurobiology · 2024Pooled it
- Clinical features of neuronal intranuclear inclusion disease with seizures: a systematic literature review.Frontiers in neurology · 2024Pooled it
- Structural Polymorphism of polyG Inclusions Revealed by In Situ Cryo-Electron Tomography.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- CGG Repeat Expansion in GIPC1 is Associated with Childhood-Onset Hereditary Ataxia.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Long-read sequencing for neurological disorders: opportunities, challenges, and future directions.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Targeted long-read sequencing enables comprehensive analysis of the genetic and epigenetic landscape of inherited myopathies.Nature communications · 2026Article
- CGG repeat expansions in Charcot-Marie-Tooth disease: insights from the 100 000 Genomes Project.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.Genome medicine · 2026Article
- Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.Acta neuropathologica communications · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- GGC repeat expansions within new open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy.Nature genetics · 2026Article
- Precise excision of expanded GGC repeats in NOTCH2NLC via CRISPR/Cas9 for treating neuronal intranuclear inclusion disease.Nature communications · 2026Article
- Augmenting cost-effectiveness in clinical diagnosis using extended whole-exome sequencing: SNVs, SVs, and beyond.Journal of human genetics · 2026Article
- Modeling neuronal intranuclear inclusion disease: A review of animal and human-derived cellular models and mechanistic insights.Zoological research · 2025Review
- Type B Fibers: A Novel Ultrastructural Biomarker for Cognitive Impairment in Neuronal Intranuclear Inclusion Disease.Brain sciences · 2025Article
- Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan.Psychiatry and clinical neurosciences · 2025Article
- Diverse Clinical Phenotypes of Neuronal Intranuclear Inclusion Disease in South Korea.Journal of clinical neurology (Seoul, Korea) · 2025Article
- Kearns-Sayre syndrome with restricted diffusion in subcortical white matter and extraocular muscle atrophy.Radiology case reports · 2025Article
- Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux.Autophagy · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal and distal limb muscle involvement. Trinucleotide repeat expansions in LRP12 or GIPC1 were recently reported to be associated with OPDM. However, a significant portion of OPDM patients have unknown genetic causes. In this study, long-read whole-genome sequencing and repeat-primed PCR were performed and we identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3). Methylation analysis indicated that methylation levels of the NOTCH2NLC gene were unaltered in OPDM3 patients, but increased significantly in asymptomatic carriers. Quantitative real-time PCR analysis indicated that NOTCH2NLC mRNA levels were increased in muscle but not in blood of OPDM3 patients. Immunofluorescence on OPDM muscle samples and expressing mutant NOTCH2NLC with (GGC)69 repeat expansions in HEK293 cells indicated that mutant NOTCH2NLC-polyglycine protein might be a major component of intranuclear inclusions, and contribute to toxicity in cultured cells. In addition, two RNA-binding proteins, hnRNP A/B and MBNL1, were both co-localized with p62 in intranuclear inclusions in OPDM muscle samples. These results indicated that a toxic protein gain-of-function mechanism and RNA gain-of-function mechanism may both play a vital role in the pathogenic processes of OPDM3. This study extended the spectrum of NOTCH2NLC repeat expansion-related diseases to a predominant myopathy phenotype presenting as OPDM, and provided evidence for possible pathogenesis of these diseases.
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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.