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We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for <jats:italic>RYR1<\/jats:italic> mutation. At least one <jats:italic>RYR1<\/jats:italic> 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 <jats:italic>RYR1<\/jats:italic> 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 <jats:italic>RYR1<\/jats:italic> 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 <jats:italic>RYR1<\/jats:italic> mutations. Further improvement in the comprehension of genotype\u2013phenotype 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 <jats:italic>RYR1<\/jats:italic> mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.<\/jats:p>","DOI":"10.1186\/s40478-022-01357-0","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T14:03:19Z","timestamp":1650031399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population 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We report here the Ethics Committee approvals of the two senior authors: the study was approved by the Ethical Committee of the Istituto Giannina Gaslini Genova on March 10, 2009 (number 567 DSc\/fg) and by the Ethical Committee of the University of Padova\u2014Hospital on May 11, 2009 (number 1879P\/0025745).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent has been obtained from the patients to publish this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}