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.
Similar content being viewed by others
References
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
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
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
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
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
Cope MJ, Whisstock J, Rayment I, Kendrick-Jones J (1996) Conservation within the myosin motor domain: implications for structure and function. Structure 4:969–987
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
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
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
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
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
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
Fujii J, Otsu K, Zorzato F et al (1991) Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253:448–451
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
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
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
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
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
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
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
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
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
Mah JK, Joseph JT (2016) An overview of congenital myopathies. Continuum (Minneap Minn) 22:1932–1953. https://doi.org/10.1212/CON.0000000000000404
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
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
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
Morales-Briceño H, Fois AF, Fung VSC (2018) Tremor. Handbook of clinical neurology. Elsevier, Amsterdam, pp 283–301
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
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
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
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
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
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 Mutation
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
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
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
Wang L, Geist J, Grogan A et al (2018) Thick filament protein network, functions, and disease association. Comprehensive physiology. Wiley, Hoboken, pp 631–709
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
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
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
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
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
Internet resources
Human Protein Atlas available from www.proteinatlas.org
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.).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict to declare.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Stavusis, J., Geist, J. & Kontrogianni-Konstantopoulos, A. Sarcomeric myopathies associated with tremor: new insights and perspectives. J Muscle Res Cell Motil 41, 285–295 (2020). https://doi.org/10.1007/s10974-019-09559-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10974-019-09559-1