ArticlePLoS genetics2013
Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy.
Article in PLoS genetics, 2013. 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 48 papers.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity.International journal of molecular sciences · 2025Article
- BIN1 gene replacement reverses BIN1-related centronuclear myopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Early Stage Morphogenesis of Transverse Tubules in Rat Cardiomyocytes: The Role of pBIN1.Circulation research · 2025Article
- Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.American journal of physiology. Heart and circulatory physiology · 2025Review
- Aligning with the 3Rs: alternative models for research into muscle development and inherited myopathies.BMC veterinary research · 2024Review
- Coupling of Alzheimer's Disease Genetic Risk Factors with Viral Susceptibility and Inflammation.Aging and disease · 2024Review
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Shaping transverse-tubules: central mechanisms that play a role in the cytosol zoning for muscle contraction.Journal of biochemistry · 2024Review
- RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.iScience · 2023Article
- MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy.Brain : a journal of neurology · 2023Article
- Proteomic insight into human directed selection of the domesticated chicken Gallus gallus.PloS one · 2023Article
- X-linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat.Journal of veterinary internal medicine · 2022Article
- Article
- AnGenes · 2022Article
- The synaptosome-associated protein 23 (SNAP23) is necessary for proper myogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants.International journal of molecular sciences · 2022Review
- A dog model for centronuclear myopathy carrying the most common DNM2 mutation.Disease models & mechanisms · 2022Article
- Alternative splicing regulation of membrane trafficking genes during myogenesis.RNA (New York, N.Y.) · 2022Article
- Mice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issuedCowling, Belinda [corrected to Cowling, Belinda S]
Authors and funding
14 authors at 10 institutions in 4 countries.
Funding
Abstract
Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies.
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