ArticleAnnals of neurology2009
Mutation in BAG3 causes severe dominant childhood muscular dystrophy.
Article in Annals of neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.
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Who cites it
183 citing papers in PubMed, 1 synthesis or guideline pooled it, 361 citations in OpenAlex.
- Guideline
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- Genetic vulnerability and dynamic mechanical stress synergistically drive sarcomere failure in human iPSC-derived cardiomyocytes.Materials today. Bio · 2026Article
- Deletion of Murine Endothelial <italic>Bag3</italic> Alters the Cellular Proteome among Organs of Origin.Journal of vascular research · 2026Article
- Blockage of autophagy causes severe skeletal muscle disruption in a mouse model for myofibrillar myopathy 6.Nature communications · 2026Article
- Autophagy activation via BAG3 gene therapy improves phenotype in a mouse model of LGMD1A.Molecular therapy. Advances · 2026Article
- Carbonic Anhydrase 3 Overexpression Modulates Signalling Pathways Associated with Cellular Stress Resilience and Proteostasis.International journal of molecular sciences · 2025Article
- Disease spectrum and long-term prognosis of patients with BAG3-associated neuromuscular diseases in Europe.Brain : a journal of neurology · 2025Article
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- Novel HSPB8 mutations in severe early-onset myopathy with involvement of respiratory and cardiac muscles cause proteostasis defects in cell models.European journal of human genetics : EJHG · 2025Article
- Phosphorylation of CRYAB induces a condensatopathy to worsen post-myocardial infarction left ventricular remodeling.The Journal of clinical investigation · 2025Article
- Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy.Acta neuropathologica · 2024Article
- Distal hereditary motor neuronopathy as a new phenotype associated with variants in BAG3.Journal of neurology · 2024Article
- Anaesthetic management of caesarean section in a patient with myofibrillar myopathy.BMJ case reports · 2023Article
- The Genetic Evaluation of Dilated Cardiomyopathy.Structural heart : the journal of the Heart Team · 2023Review
- HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.Autophagy · 2023Article
- Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveMyofibrillar myopathies (MFMs) are morphologically distinct but genetically heterogeneous muscular dystrophies in which disintegration of Z disks and then of myofibrils is followed by ectopic accumulation of multiple proteins. Cardiomyopathy, neuropathy, and dominant inheritance are frequent associated features. Mutations in alphaB-crystallin, desmin, myotilin, Zasp, or filamin-C can cause MFMs and were detected in 32 of 85 patients of the Mayo MFM cohort. Bag3, another Z-disk-associated protein, has antiapoptotic properties, and its targeted deletion in mice causes fulminant myopathy with early lethality. We therefore searched for mutations in BAG3 in 53 unrelated MFM patients.
methodsWe searched for mutations in BAG3 by direct sequencing. We analyzed structural changes in muscle by histochemistry, immunocytochemistry, and electron microscopy, examined mobility of the mutant Bag3 by nondenaturing electrophoresis, and searched for abnormal aggregation of the mutant protein in COS-7 (SV-40 transformed monkey kidney fibroblast-7) cells.
resultsWe identified a heterozygous p.Pro209Leu mutation in three patients. All presented in childhood, had progressive limb and axial muscle weakness, and experienced development of cardiomyopathy and severe respiratory insufficiency in their teens; two had rigid spines, and one a peripheral neuropathy. Electron microscopy showed disintegration of Z disks, extensive accumulation of granular debris and larger inclusions, and apoptosis of 8% of the nuclei. On nondenaturing electrophoresis of muscle extracts, the Bag3 complex migrated faster in patient than control extracts, and expression of FLAG-labeled mutant and wild-type Bag3 in COS cells showed abnormal aggregation of the mutant protein.
interpretationWe conclude mutation in Bag3 defines a novel severe autosomal dominant childhood muscular dystrophy.
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