ArticleJCI insight2022
A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2-directed myogenesis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Disease-associated mutations inbioRxiv : the preprint server for biology · 2026Article
- Spaceflight alters molecular networks linked to diverse human diseases in a single cellular model.Science advances · 2026Article
- Fine-tuning striated muscle performance: conserved sarcomere-level mechanisms across insect and vertebrate systems.Frontiers in physiology · 2026Review
- TPM2 regulates contractility and biomechanical properties in trabecular meshwork cells.Scientific reports · 2025Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Myotube Guidance: Shaping up the Musculoskeletal System.Journal of developmental biology · 2024Review
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Glutamate 139 of tropomyosin is critical for cardiac thin filament blocked-state stabilization.Journal of molecular and cellular cardiology · 2024Article
- Bulk and single-cell alternative splicing analyses reveal roles of TRA2B in myogenic differentiation.Cell proliferation · 2024Article
- The serine/threonine kinase Back seat driver prevents cell fusion to maintain cell identity.Developmental biology · 2023Article
- Case report: Exome sequencing revealed disease-causing variants in a patient with spondylospinal thoracic dysostosis.Frontiers in pediatrics · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Transient overexpression of the 4 variants also disrupted the morphogenesis of mouse myotubes in vitro and negatively affected zebrafish muscle development in vivo. We used transient overexpression assays in zebrafish to characterize 2 potentially novel TPM2 variants and 1 recurring variant that we identified in patients with DA (V129A, E139K, A155T, respectively) and found these variants caused musculoskeletal defects similar to those of known pathogenic variants. The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders and that our myogenic assays can predict the clinical severity of TPM2 variants.
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