ArticleHuman molecular genetics2009
Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00272883 (Molecular Analysis of Neuromuscular Disease), which is not on this map. Cited by 108 papers.
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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.
The trial behind it
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.
Molecular Analysis of Neuromuscular Disease
Who cites it
108 citing papers in PubMed, 143 citations in OpenAlex.
- Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation.American journal of physiology. Lung cellular and molecular physiology · 2014Trial
- Alterations of actin in aging.Journal of cell science · 2026Review
- Mechanism of actin thin filament pointed-end elongation by leiomodin.Nature communications · 2026Article
- Coordinated Bone-Muscle Axis Association in South China Carp (Foods (Basel, Switzerland) · 2026Article
- The D2.B10-DmdThe American journal of pathology · 2026Article
- Clinical, Histological, and Genetic Characterization of a Large Cohort of 49 Patients With Nebulin-Related Congenital Myopathy.Human mutation · 2026Article
- Retrospective Cohort Analysis of Clinical, Molecular, and Histopathologic Characteristics of 275 Patients With Nemaline Myopathy.Neurology. Genetics · 2025Article
- Pathogenic TNNT1 variants are associated with aberrant thin filament compliance and myofibre hyper-contractility.The Journal of physiology · 2025Article
- Generation of a novel mouse model of nemaline myopathy due to recurrent NEB exon 55 deletion.Skeletal muscle · 2025Article
- Generation of a novel mouse model of nemaline myopathy due to recurrentResearch square · 2024Article
- Paraspinal muscle fibre structural and contractile characteristics demonstrate distinct irregularities in patients with spinal degeneration and deformity.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024Article
- Comprehensive phenotypic characterization of an allelic series of zebrafish models of NEB-related nemaline myopathy.Human molecular genetics · 2024Article
- Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects.Acta neuropathologica · 2024Article
- Recessive TMOD1 mutation causes childhood cardiomyopathy.Communications biology · 2024Article
- A nemaline myopathy-linked mutation inhibits the actin-regulatory functions of tropomodulin and leiomodin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Aberrations in Energetic Metabolism and Stress-Related Pathways Contribute to Pathophysiology in the Neb Conditional Knockout Mouse Model of Nemaline Myopathy.The American journal of pathology · 2023Article
- Drosophila Tropomodulin is required for multiple actin-dependent processes within developing myofibers.Development (Cambridge, England) · 2023Article
- NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy.Acta neuropathologica communications · 2022Article
- Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.International journal of molecular sciences · 2022Article
- The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022Review
48 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Nemaline myopathy (NM) is the most common non-dystrophic congenital myopathy. Clinically the most important feature of NM is muscle weakness; however, the mechanisms underlying this weakness are poorly understood. Here, we studied the muscular phenotype of NM patients with a well-defined nebulin mutation (NM-NEB), using a multidisciplinary approach to study thin filament length regulation and muscle contractile performance. SDS-PAGE and western blotting revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward-shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and non-uniform thin filament lengths in NM-NEB muscle compared with control muscle. Immunofluorescence confocal microscopy and electron microscopy studies indicated that average thin filament length is reduced from approximately 1.3 microm in control muscle to approximately 0.75 microm in NM-NEB muscle. Thus, the present study is the first to show a distinct genotype-functional phenotype correlation in patients with NM due to a nebulin mutation, and provides evidence for the notion that dysregulated thin filament length contributes to muscle weakness in NM patients with nebulin mutations. Furthermore, a striking similarity between the contractile and structural phenotypes of nebulin-deficient mouse muscle and human NM-NEB muscle was observed, indicating that the nebulin knockout model is well suited for elucidating the functional basis of muscle weakness in NM and for the development of treatment strategies.
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Registered trials
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