Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study.
| Title: | Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study. |
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| Authors: | Fusto A; Department of Neurosciences DNS, University of Padova, 35128, Padua, Italy.; Cassandrini D; Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Fiorillo C; Paediatric Neurology and Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16147, Genoa, Italy.; Codemo V; Department of Neurosciences DNS, University of Padova, 35128, Padua, Italy.; Astrea G; Department of Neuroscience, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; D'Amico A; Molecular Medicine Unit, Ospedale Bambin Gesù, 00165, Rome, Italy.; Maggi L; Neuroimmunology and Neuromuscular Disorders Unit, Foundation IRCCS Neurological Institute 'C. Besta', 20133, Milan, Italy.; Magri F; Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, I.R.C.C.S. Foundation Cà Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy.; Pane M; Department of Paediatric Neurology, Catholic University, 00165, Rome, Italy.; Tasca G; Unità Operativa Complessa Di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.; Sabbatini D; Department of Neurosciences DNS, University of Padova, 35128, Padua, Italy.; Bello L; Department of Neurosciences DNS, University of Padova, 35128, Padua, Italy.; Battini R; Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Bernasconi P; Neuroimmunology and Neuromuscular Disorders Unit, Foundation IRCCS Neurological Institute 'C. Besta', 20133, Milan, Italy.; Fattori F; Department of Neuroscience, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Bertini ES; Department of Neuroscience, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Comi G; Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, I.R.C.C.S. Foundation Cà Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy.; Messina S; Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, 98122, Messina, Italy.; Mongini T; SG. Battista Hospital, Neuromuscular Center, University of Turin, 10124, Turin, Italy.; Moroni I; Child Neurology Department, Neurological Institute C. Besta Foundation IRCCS, 20133, Milan, Italy.; Panicucci C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16147, Genova, Italy.; Berardinelli A; Child and Adolescent Unit, IRCCS C. Mondino Foundation, 27100, Pavia, Italy.; Donati A; Metabolic Disease Unit, AOU Meyer Children Hospital, 50139, Florence, Italy.; Nigro V; 'Luigi Vanvitelli' University and Telethon Institute of Genetics and Medicine (TIGEM), 80078, Naples, Italy.; Pini A; Child Neurology and Psychiatry Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.; Giannotta M; Child Neurology and Psychiatry Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.; Dosi C; Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Ricci E; Department of Paediatric Neurology, Catholic University, 00165, Rome, Italy.; Mercuri E; Department of Paediatric Neurology, Catholic University, 00165, Rome, Italy.; Minervini G; Department of Biomedical Sciences, University of Padova, 35128, Padua, Italy.; Tosatto S; Department of Biomedical Sciences, University of Padova, 35128, Padua, Italy.; Santorelli F; Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56128, Pisa, Italy.; Bruno C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16147, Genova, Italy. claudio2246@gmail.com.; Pegoraro E; Department of Neurosciences DNS, University of Padova, 35128, Padua, Italy. elena.pegoraro@unipd.it. |
| Source: | Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Apr 15; Vol. 10 (1), pp. 54. Date of Electronic Publication: 2022 Apr 15. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2013]- |
| MeSH Terms: | Myopathies, Structural, Congenital*/genetics ; Myopathies, Structural, Congenital*/pathology ; Myopathy, Central Core*/genetics ; Myopathy, Central Core*/pathology ; Ryanodine Receptor Calcium Release Channel*/genetics; Muscle, Skeletal/pathology ; Mutation/genetics ; Humans |
| Abstract: | 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.; (© 2022. The Author(s).) |
| References: | J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254); Nature. 2015 Jan 1;517(7532):50-55. (PMID: 25517095); J Gen Physiol. 2001 Sep;118(3):277-90. (PMID: 11524458); Hum Mol Genet. 2019 Jun 1;28(11):1872-1884. (PMID: 30689883); Neuromuscul Disord. 2005 Oct;15(9-10):577-87. (PMID: 16084090); J Biol Chem. 2000 Apr 21;275(16):11778-83. (PMID: 10766801); Neuromuscul Disord. 2015 Jul;25(7):567-76. (PMID: 25958340); Anesthesiology. 2006 Dec;105(6):1164-75. (PMID: 17122579); Hum Mutat. 2012 Jun;33(6):981-8. (PMID: 22473935); Neuromuscul Disord. 2002 Dec;12(10):930-8. (PMID: 12467748); Nucleic Acids Res. 2003 Jul 1;31(13):3625-30. (PMID: 12824381); Anesthesiology. 2018 Jan;128(1):159-167. (PMID: 28902673); J Phys Chem B. 2005 Aug 18;109(32):15598-610. (PMID: 16852978); Hum Mutat. 2005 Nov;26(5):413-25. (PMID: 16163667); Anesthesiology. 2008 Oct;109(4):625-8. (PMID: 18813041); Am J Hum Genet. 2002 Oct;71(4):739-49. (PMID: 12192640); Genomics. 1991 Nov;11(3):751-5. (PMID: 1774074); Brain. 2006 Jun;129(Pt 6):1470-80. (PMID: 16621918); Brain. 2005 Jan;128(Pt 1):42-51. (PMID: 15548556); J Biol Chem. 1993 Jun 25;268(18):13414-21. (PMID: 7685761); Neurology. 2005 Dec 27;65(12):1930-5. (PMID: 16380615); Bioinformatics. 2020 Dec 16;:. (PMID: 33325498); Hum Mutat. 2009 Apr;30(4):E575-90. (PMID: 19191333); J Neuropathol Exp Neurol. 2007 Jan;66(1):57-65. (PMID: 17204937); Neuromuscul Disord. 2002 Aug;12(6):588-95. (PMID: 12117485); Cell Calcium. 2002 Sep;32(3):143-51. (PMID: 12208234); Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83. (PMID: 17452350); Bioinformatics. 2012 Aug 15;28(16):2189-90. (PMID: 22711791); Neurogenetics. 2012 May;13(2):115-24. (PMID: 22371254); Nat Commun. 2015 Aug 06;6:7947. (PMID: 26245150); J Mol Biol. 2000 Sep 8;302(1):205-17. (PMID: 10964570); J Biol Chem. 2012 Sep 14;287(38):31624-32. (PMID: 22822064); IUBMB Life. 2007 Jan;59(1):14-20. (PMID: 17365175); Subcell Biochem. 2018;87:329-352. (PMID: 29464565); Anaesth Intensive Care. 2008 May;36(3):391-403. (PMID: 18564801); Bioinformatics. 2017 Jun 15;33(12):1889-1891. (PMID: 28186245); Neuromuscul Disord. 2003 Feb;13(2):151-7. (PMID: 12565913); J Histochem Cytochem. 2000 May;48(5):623-9. (PMID: 10769046); Nucleic Acids Res. 2000 Jan 1;28(1):235-42. (PMID: 10592235); Anesth Analg. 1992 Sep;75(3):441-8. (PMID: 1510267); Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16725-30. (PMID: 12486242); Anesthesiology. 2011 Nov;115(5):938-45. (PMID: 21918424); J Neurol. 2015 Jul;262(7):1728-40. (PMID: 25957634); J Biol Chem. 2001 May 18;276(20):16931-5. (PMID: 11279144); BMC Genomics. 2019 Jun 13;20(1):492. (PMID: 31195974); Int J Biochem Cell Biol. 2009 Mar;41(3):677-86. (PMID: 18761102); Hum Mol Genet. 2006 Sep 15;15(18):2791-803. (PMID: 16940308); Orphanet J Rare Dis. 2007 Jul 13;2:31. (PMID: 17631035); Hum Mol Genet. 2014 Feb 15;23(4):980-91. (PMID: 24105469); Neurology. 2008 Jan 8;70(2):114-22. (PMID: 17538032); Dis Model Mech. 2019 Dec 19;12(12):. (PMID: 31874912); Eur J Hum Genet. 2014 Jun;22(6):801-8. (PMID: 24193343); Hum Mol Genet. 2001 Dec 1;10(25):2879-87. (PMID: 11741831); Ann Neurol. 2010 Nov;68(5):717-26. (PMID: 20839240); Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. (PMID: 30395287); Nucleic Acids Res. 2012 Jul;40(Web Server issue):W452-7. (PMID: 22689647); Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4164-9. (PMID: 10097181); Am J Hum Genet. 2006 Nov;79(5):859-68. (PMID: 17033962); Orphanet J Rare Dis. 2013 Aug 06;8:117. (PMID: 23919265); Sci Transl Med. 2017 Apr 19;9(386):. (PMID: 28424332); Semin Pediatr Neurol. 2011 Dec;18(4):239-49. (PMID: 22172419); Hum Mutat. 2006 Oct;27(10):977-89. (PMID: 16917943); F1000Res. 2018 Nov 27;7:. (PMID: 30542613); Nucleic Acids Res. 2016 Jul 8;44(W1):W367-74. (PMID: 27198219); Biochemistry. 1997 Sep 23;36(38):11496-503. (PMID: 9298970); J Biol Chem. 2003 Jul 11;278(28):25722-30. (PMID: 12732639); Hum Mutat. 2002 Aug;20(2):88-97. (PMID: 12124989); Methods Mol Biol. 2017;1654:39-54. (PMID: 28986782); Neuromuscul Disord. 2016 Jan;26(1):21-5. (PMID: 26631338); J Clin Neurosci. 2019 Apr;62:238-239. (PMID: 30612914); Brain. 2003 Nov;126(Pt 11):2341-9. (PMID: 12937085); Hum Mutat. 2006 Aug;27(8):830. (PMID: 16835904); Acta Neuropathol Commun. 2019 Jan 5;7(1):3. (PMID: 30611313); Brain. 1956 Dec;79(4):610-21. (PMID: 13396066); J Biol Chem. 2002 Feb 22;277(8):6530-5. (PMID: 11726651); Pediatr Neurol. 2014 Aug;51(2):275-8. (PMID: 24950660); J Biol Chem. 1997 Oct 17;272(42):26332-9. (PMID: 9334205); Am J Physiol Cell Physiol. 2011 May;300(5):C998-C1012. (PMID: 21289290); Bioinformatics. 2009 May 1;25(9):1189-91. (PMID: 19151095); Bioinformatics. 2020 Mar 1;36(6):1765-1771. (PMID: 31697312); Neurology. 2002 Jul 23;59(2):284-7. (PMID: 12136074); Hum Mol Genet. 2001 Oct 15;10(22):2581-92. (PMID: 11709545); Cell. 2016 Sep 22;167(1):145-157.e17. (PMID: 27662087); Nat Genet. 1993 Sep;5(1):51-5. (PMID: 8220423); Nucleic Acids Res. 1997 Sep 1;25(17):3389-402. (PMID: 9254694); Curr Opin Pharmacol. 2008 Jun;8(3):319-26. (PMID: 18313359); J Physiol. 2003 Mar 15;547(Pt 3):807-23. (PMID: 12562929); J Biol Chem. 2003 Jun 20;278(25):22600-8. (PMID: 12704193); Neuromuscul Disord. 2001 Sep;11(6-7):530-7. (PMID: 11525881); Neuromuscul Disord. 2012 May;22(5):453-62. (PMID: 22226685); Eur J Pediatr. 2014 Dec;173(12):1691-4. (PMID: 24706162); Hum Mol Genet. 2000 Nov 1;9(18):2599-608. (PMID: 11063719); Proteins. 2006 Mar 1;62(4):1125-32. (PMID: 16372356); Neuromuscul Disord. 2012 Dec;22(12):1096-104. (PMID: 22784669); Ann Neurol. 2002 Jun;51(6):750-9. (PMID: 12112081); Neurology. 2000 Dec 12;55(11):1689-96. (PMID: 11113224); Neurosci Lett. 2014 Apr 30;566:32-5. (PMID: 24561095); Can J Anaesth. 2011 Jun;58(6):504-13. (PMID: 21455645); Neuromuscul Disord. 2021 Oct;31(10):968-977. (PMID: 34627702); Curr Protoc Hum Genet. 2013 Jan;Chapter 7:Unit7.20. (PMID: 23315928); Am J Hum Genet. 2020 Dec 3;107(6):1078-1095. (PMID: 33217308); Genet Med. 2021 Jul;23(7):1288-1295. (PMID: 33767344); Neuromuscul Disord. 2013 Feb;23(2):120-32. (PMID: 23183335); Eur J Neurol. 2008 Apr;15(4):e31-2. (PMID: 18312400); Nat Commun. 2019 Feb 15;10(1):797. (PMID: 30770808); Genome Biol. 2007;8(11):R232. (PMID: 17976239); Hum Mol Genet. 2018 Jul 1;27(13):2367-2382. (PMID: 29701772); Muscle Nerve. 2006 Jun;33(6):715-31. (PMID: 16477617); Biochemistry. 2007 Apr 10;46(14):4272-9. (PMID: 17361990); Orphanet J Rare Dis. 2014 Jan 16;9:8. (PMID: 24433488) |
| Contributed Indexing: | Keywords: Central core disease; Genotype–phenotype correlations; Multi-minicore disease; Neuromuscular disorder; Protein modelling; RYR1-related myopathies |
| Substance Nomenclature: | 0 (RYR1 protein, human); 0 (Ryanodine Receptor Calcium Release Channel) |
| Entry Date(s): | Date Created: 20220416 Date Completed: 20220419 Latest Revision: 20220716 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9013059 |
| DOI: | 10.1186/s40478-022-01357-0 |
| PMID: | 35428369 |
| Database: | MEDLINE |
Journal Article