ArticleJournal of neuromuscular diseases2015
Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein.
Article in Journal of neuromuscular diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Two journeys, one diagnosis: exploring the clinical outcomes of twins with congenital myopathy.BMC neurology · 2025Article
- Limited pre-clinical relevance of the heterozygous RYR1-I4895T/+ mouse model due to its mild phenotype.Journal of neuromuscular diseases · 2025Article
- Dual role of the S5 segment in type 1 ryanodine receptor channel gating.Communications biology · 2024Article
- Functional benefit of CRISPR-Cas9-induced allele deletion forMolecular therapy. Nucleic acids · 2024Article
- Huntingtin regulates calcium fluxes in skeletal muscle.The Journal of general physiology · 2023Article
- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Identification of ER/SR resident proteins as biomarkers for ER/SR calcium depletion in skeletal muscle cells.Orphanet journal of rare diseases · 2022Article
- Targeted transcript analysis in muscles from patients with genetically diverse congenital myopathies.Brain communications · 2022Article
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
- In vivo RyR1 reduction in muscle triggers a core-like myopathy.Acta neuropathologica communications · 2020Article
- Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.Orphanet journal of rare diseases · 2020Article
- Cored in the act: the use of models to understand core myopathies.Disease models & mechanisms · 2019Review
- Mouse model of severe recessive RYR1-related myopathy.Human molecular genetics · 2019Article
- 'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.Acta neuropathologica communications · 2019Article
- Excitation-Contraction Coupling Alterations in Myopathies.Journal of neuromuscular diseases · 2016Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCentral Core Disease (CCD) is a congenital myopathy often resulting from a mutation in RYR1 gene. Mutations in RyR1 can increase or decrease channel activity, or induce a reduction in the amount of protein. The consequences of a single mutation are sometimes multiple and the analysis of the functional effects is complex.
objectiveThe consequences of the p.Y4864H mutation identified in a CCD patient have been studied regarding both RyR1 function and amount.
methodsThe amount of RyR1 in human and mouse muscles was evaluated using qRT-PCR and quantitative Western blot, and calcium release was studied using calcium imaging on primary cultures. The results were compared between human and mouse.
resultsThe p.Y4864H mutation induced an alteration of calcium release, and in addition was associated to a reduction in the amount of RyR1 in the patient's muscle. This suggests two possible pathophysiological mechanisms: the alteration of calcium release could result from a modification of the channel properties of RyR1 or from a RyR1 reduction. In order to discriminate between the two hypotheses, we used the heterozygous RyR1 knockout (RyR1+/-) mouse model showing a comparable RyR1 protein reduction. No reduction in calcium release was observed in primary muscle culture from these mice, and no muscle weakness was measured.
conclusionsBecause the reduction in the amount of RyR1 protein has no functional consequences in the murine model, the muscle weakness observed in the patient is most likely the result of a modification of the calcium channel function of RyR1 due to the p.Y4864H mutation.
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