Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study

Aurora Fusto, Denise Cassandrini, Chiara Fiorillo, Claudio Fiorillo, Valentina Codemo, Guja Astrea, Adele D’Amico, Adele D'Amico, Lorenzo Maggi, Francesca Magri, Marika Pane, Giorgio Tasca, Daniele Sabbatini, Luca Bello, Roberta Battini, Pia Bernasconi, Fabiana Fattori, Francesco Fattori, Enrico Silvio Bertini, Giacomo ComiSonia Messina, Tiziana Mongini, Isabella Moroni, Chiara Panicucci, Angela Berardinelli, Alice Donati, Vincenzo Nigro, Antonella Pini, Melania Giannotta, Claudia Dosi, Enzo Ricci, Eugenio Maria Mercuri, Giovanni Minervini, Silvio Tosatto, Filippo Santorelli, Claudio Bruno, Elena Pegoraro

Risultato della ricerca: Contributo in rivistaArticolo in rivista


Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaActa neuropathologica communications
Stato di pubblicazionePubblicato - 2022


  • Central core disease
  • Genotype–phenotype correlations
  • Multi-minicore disease
  • Neuromuscular disorder
  • Protein modelling
  • RYR1-related myopathies


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