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Sarcomeric myopathies associated with tremor: new insights and perspectives

  • Janis Stavusis
  • Janelle Geist
  • Aikaterini Kontrogianni-KonstantopoulosEmail author
Article
  • 39 Downloads

Abstract

Myopathies are a large and heterogeneous group of disorders associated with mutations in structural and regulatory genes responsible for proper muscle assembly, organization and function. Despite the molecular diversity of inherited myopathies, they have historically been classified by the phenotypic traits observed in affected patients. It is therefore common for myopathies originating from mutations in different genes to be grouped together due to similar physical manifestations, and conversely myopathies resulting from mutations in the same gene to be considered separately due to disparate symptoms. Herein, we focus on an early onset myopathy linked to inherited or de novo mutations in sarcomeric genes that is characterized by muscle weakness, hypotonia and tremor, and further highlight that it may constitute a new form of myopathy, with tremor as its defining feature. Based on recent reports, we also discuss the possible myogenic origin of the tremor that may start at the level of the sarcomere due to structural and/or contractile alterations occurring as a result of the identified mutations. It is our hope that establishment of this form of myopathy accompanied by myogenic tremor as a new disease entity will have important diagnostic and therapeutic implications.

Keywords

Sarcomeric genes Congenital myopathy Muscle weakness Hypotonia Tremor 

Notes

Acknowledgments

This work was supported by the Fulbright Scholar Program (to JS), NIH (Training Program in Muscle Biology, T32 AR007592-17 to J.G. and R21AR072981 to A.K.K.), and the Muscular Dystrophy Association (Research Grant 313579 to A.K.K.).

Compliance with ethical standards

Conflict of interest

The authors have no conflict to declare.

References

  1. Abdulhaq UN, Daana M, Dor T et al (2016) Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1). Muscle Nerve 53:564–569.  https://doi.org/10.1002/mus.24885 CrossRefPubMedGoogle Scholar
  2. Ackermann MA, Kerr JP, King B et al (2015) The phosphorylation profile of myosin binding protein-C slow is dynamically regulated in slow-twitch muscles in health and disease. Sci Rep 5:12637.  https://doi.org/10.1038/srep12637 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ackermann MA, Kontrogianni-Konstantopoulos A (2011) Myosin binding protein-C: a regulator of actomyosin interaction in striated muscle. J Biomed Biotechnol 2011:636403.  https://doi.org/10.1155/2011/636403 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ackermann MA, Kontrogianni-Konstantopoulos A (2013) Myosin binding protein-C slow: a multifaceted family of proteins with a complex expression profile in fast and slow twitch skeletal muscles. Front Physiol 4:391.  https://doi.org/10.3389/fphys.2013.00391 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Ackermann MA, Patel PD, Valenti J et al (2013) Loss of actomyosin regulation in distal arthrogryposis myopathy due to mutant myosin binding protein-C slow. FASEB J 27:3217–3228.  https://doi.org/10.1096/fj.13-228882 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cope MJ, Whisstock J, Rayment I, Kendrick-Jones J (1996) Conservation within the myosin motor domain: implications for structure and function. Structure 4:969–987CrossRefGoogle Scholar
  7. Cullup T, Lamont PJ, Cirak S et al (2012) Mutations in MYH7 cause multi-minicore disease (MmD) with variable cardiac involvement. Neuromuscul Disord 22:1096–1104.  https://doi.org/10.1016/j.nmd.2012.06.007 CrossRefPubMedGoogle Scholar
  8. de Tombe PP (2006) Myosin binding protein C in the heart. Circ Res 98:1234–1236.  https://doi.org/10.1161/01.RES.0000225873.63162.c4 CrossRefPubMedGoogle Scholar
  9. Donkervoort S, Papadaki M, de Winter JM et al (2015) TPM 3 deletions cause a hypercontractile congenital muscle stiffness phenotype. Ann Neurol 78:982–994.  https://doi.org/10.1002/ana.24535 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Edgerton VR, Roy RR, Allen DL, Monti RJ (2002) Adaptations in skeletal muscle disuse or decreased-use atrophy. Am J Phys Med Rehabil 81:S127–S147.  https://doi.org/10.1097/01.PHM.0000029778.56440.90 CrossRefPubMedGoogle Scholar
  11. Evans JM, Cox ML, Huska J et al (2016) Exome sequencing reveals a nebulin nonsense mutation in a dog model of nemaline myopathy. Mamm Genome 27:495–502.  https://doi.org/10.1007/s00335-016-9644-9 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Fiorillo C, Astrea G, Savarese M et al (2016) MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. Orphanet J Rare Dis 11:91.  https://doi.org/10.1186/s13023-016-0476-1 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Fujii J, Otsu K, Zorzato F et al (1991) Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253:448–451CrossRefGoogle Scholar
  14. Galińska-Rakoczy A, Engel P, Xu C et al (2008) Structural basis for the regulation of muscle contraction by troponin and tropomyosin. J Mol Biol 379:929–935.  https://doi.org/10.1016/j.jmb.2008.04.062 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Geist J, Kontrogianni-Konstantopoulos A (2016) MYBPC1, an emerging myopathic gene: what we know and what we need to learn. Front Physiol 7:410.  https://doi.org/10.3389/fphys.2016.00410 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Grey C, Méry A, Pucéat M (2005) Fine-tuning in Ca2+ homeostasis underlies progression of cardiomyopathy in myocytes derived from genetically modified embryonic stem cells. Hum Mol Genet 14:1367–1377.  https://doi.org/10.1093/hmg/ddi146 CrossRefPubMedGoogle Scholar
  17. Jin J-P, Brotto MA, Hossain MM et al (2003) Truncation by Glu 180 Nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy. J Biol Chem 278:26159–26165.  https://doi.org/10.1074/jbc.M303469200 CrossRefPubMedGoogle Scholar
  18. Johnston JJ, Kelley RI, Crawford TO et al (2000) A novel nemaline myopathy in the amish caused by a mutation in troponin T1. Am J Hum Genet 67:814–821.  https://doi.org/10.1086/303089 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kontrogianni-Konstantopoulos A, Ackermann MA, Bowman AL et al (2009) Muscle giants: molecular scaffolds in sarcomerogenesis. Physiol Rev 89:1217–1267.  https://doi.org/10.1152/physrev.00017.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Lamont PJ, Udd B, Mastaglia FL et al (2006) Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy. J Neurol Neurosurg Psychiatry 77:208–215.  https://doi.org/10.1136/jnnp.2005.073825 CrossRefPubMedGoogle Scholar
  21. Lefter S, Hardiman O, McLaughlin RL et al (2015) A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family. Neuromuscul Disord 25:155–160.  https://doi.org/10.1016/j.nmd.2014.09.007 CrossRefPubMedGoogle Scholar
  22. Li S, Hong M (2011) Protonation, tautomerization, and rotameric structure of histidine: a comprehensive study by magic-angle-spinning solid-state NMR. J Am Chem Soc 133:1534.  https://doi.org/10.1021/JA108943N CrossRefPubMedPubMedCentralGoogle Scholar
  23. Mah JK, Joseph JT (2016) An overview of congenital myopathies. Continuum (Minneap Minn) 22:1932–1953.  https://doi.org/10.1212/CON.0000000000000404 CrossRefGoogle Scholar
  24. Marra JD, Engelstad KE, Ankala A et al (2015) Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order Amish. Muscle Nerve 51:767–772.  https://doi.org/10.1002/mus.24528 CrossRefPubMedGoogle Scholar
  25. Martinsson T, Oldfors A, Darin N et al (2000) Autosomal dominant myopathy: missense mutation (Glu-706 → Lys) in the myosin heavy chain IIa gene. Proc Natl Acad Sci USA 97:14614–14619.  https://doi.org/10.1073/pnas.250289597 CrossRefPubMedGoogle Scholar
  26. Martyn DA (2004) Myosin binding protein-C: structural and functional complexity. J Mol Cell Cardiol 37:813–815.  https://doi.org/10.1016/j.yjmcc.2004.07.005 CrossRefPubMedGoogle Scholar
  27. Morales-Briceño H, Fois AF, Fung VSC (2018) Tremor. Handbook of clinical neurology. Elsevier, Amsterdam, pp 283–301Google Scholar
  28. Murgiano L, Tammen I, Harlizius B, Drögemüller C (2012) A de novo germline mutation in MYH7 causes a progressive dominant myopathy in pigs. BMC Genet 13:99.  https://doi.org/10.1186/1471-2156-13-99 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Myers CD, Goh PY, Allen TS et al (1996) Developmental genetic analysis of troponin T mutations in striated and nonstriated muscle cells of Caenorhabditis elegans. J Cell Biol 132:1061–1077.  https://doi.org/10.1083/JCB.132.6.1061 CrossRefPubMedGoogle Scholar
  30. Ottenheijm CAC, Lawlor MW, Stienen GJM et al (2011) Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy. Hum Mol Genet 20:2015–2025.  https://doi.org/10.1093/hmg/ddr084 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Richter A, Wissel J, Harlizius B et al (1995) The campus syndrome in pigs: neurological, neurophysiological, and neuropharmacological characterization of a new genetic animal model of high-frequency tremor. Exp Neurol 134:205–213.  https://doi.org/10.1006/exnr.1995.1050 CrossRefPubMedGoogle Scholar
  32. Schorling D, Kirschner J, Bönnemann C (2017) Congenital muscular dystrophies and myopathies: an overview and update. Neuropediatrics 48:247–261.  https://doi.org/10.1055/s-0037-1604154 CrossRefPubMedGoogle Scholar
  33. Shashi V, Geist J, Lee Y et al (2019) Heterozygous variants in MYBPC1 are associated with an expanded neuromuscular phenotype beyond arthrogryposis. In Press, Hum MutationCrossRefGoogle Scholar
  34. Stavusis J, Lace B, Schäfer J et al (2019) Novel mutations in MYBPC1 are associated with myogenic tremor and mild myopathy. Ann Neurol.  https://doi.org/10.1002/ana.25494 CrossRefPubMedGoogle Scholar
  35. Tajsharghi H, Stibrant Sunnerhagen K, Darin N et al (2004) Induced shift in myosin heavy chain expression in myosin myopathy by endurance training. J Neurol 251:179–183.  https://doi.org/10.1007/s00415-004-0295-5 CrossRefPubMedGoogle Scholar
  36. Uhlen M, Fagerberg L, Hallstrom BM et al (2015) Tissue-based map of the human proteome. Science(80-) 347:1260419.  https://doi.org/10.1126/science.1260419 CrossRefGoogle Scholar
  37. Wang L, Geist J, Grogan A et al (2018) Thick filament protein network, functions, and disease association. Comprehensive physiology. Wiley, Hoboken, pp 631–709CrossRefGoogle Scholar
  38. Weber FE, Vaughan KT, Reinach FC, Fischman DA (1993) Complete sequence of human fast-type and slow type muscle myosin binding protein C (MyBP-C): differential expression, conserved domain structure and chromosome assignment. Eur J Biochem 216:661–669.  https://doi.org/10.1111/j.1432-1033.1993.tb18186.x CrossRefPubMedGoogle Scholar
  39. Weterman MAJ, Barth PG, van Spaendonck-Zwarts KY et al (2013) Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy. Brain 136:282–293.  https://doi.org/10.1093/brain/aws293 CrossRefPubMedGoogle Scholar
  40. Wiedemar N, Riedi A-K, Jagannathan V et al (2015) Genetic abnormalities in a calf with congenital increased muscular tonus. J Vet Intern Med 29:1418–1421.  https://doi.org/10.1111/jvim.13599 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Wimberly B, Chazin WJ, Thulin E (1995) Characterization of the N-terminal half-saturated state of calbindin D9k: NMR studies of the N56A mutant. Protein Sci 4:1045–1055.  https://doi.org/10.1002/pro.5560040603 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wissel J, Harlizuis B, Richter A et al (1997) A new tremor mutant in the pietrain pig: an animal model of orthostatic tremor? Clinical and neurophysiological observations. Mov Disord 12:743–746.  https://doi.org/10.1002/mds.870120519 CrossRefPubMedGoogle Scholar

Internet resources

  1. Human Protein Atlas available from www.proteinatlas.org

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Latvian Biomedical Research and Study CentreRigaLatvia
  2. 2.Dept. of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA

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