{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:44:50Z","timestamp":1782996290239,"version":"3.54.5"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["113416"],"award-info":[{"award-number":["113416"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["109084"],"award-info":[{"award-number":["109084"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF-DAAD"],"award-info":[{"award-number":["NRF-DAAD"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007112","name":"University of Cape Town","doi-asserted-by":"publisher","award":["Health Sciences and Neuroscience Institute fellowships"],"award-info":[{"award-number":["Health Sciences and Neuroscience Institute fellowships"]}],"id":[{"id":"10.13039\/501100007112","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Unbiased in silico approaches applied to genome-wide data prioritized putative functional gene variants associating with treatment-resistant ophthalmoplegic myasthenia gravis (OP-MG). Although altered expression of genes harbouring these variants, or associated pathways, were shown in patient-derived transdifferentiated-myocyte models, gene expression in orbital-derived muscle was required to test the validity of the predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sampled orbicularis oculi muscle (OOM) and one paralysed extraocular muscle (EOM) from six individuals with OP-MG during blepharoptosis and re-alignment surgeries, respectively. For controls, the OOMs were sampled from four individuals without myasthenia undergoing surgery for non-muscle causes of ptosis, and one non-paralysed EOM. Using a qPCR array, expression of 120 genes was compared between OP-MG and control OOMs, profiling putative \u201cOP-MG\u201d genes, genes in related biological pathways and genes reported to be dysregulated in MG cases or experimental MG models, and in EOMs of cases with strabismus. Normalization was performed with two stable reference genes. Differential gene expression was compared between OP-MG and control samples using the \u0394\u0394CT method. Co-expression was analysed by pairwise correlation of gene transcripts to infer expression networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, transcript levels were similar in OOMs and EOMs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.72). In OOMs, significant downregulated expression of eight genes was observed in OP-MG cases compared with controls (&gt;\u2009twofold;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.016), including\n                      <jats:italic>TFAM<\/jats:italic>\n                      , a mitochondrial transcription factor, and genes related to the following pathways: atrophy signalling; muscle regeneration and contraction; glycogen synthesis; and extracellular matrix remodelling. Several microRNAs, known to be highly expressed in EOMs, are predicted to regulate some of these genes. Co-expression analyses of gene-pairs suggested high interconnectedness of gene expression networks in OP-MG muscle, but not controls (r\u2009&gt;\u20090.96,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Significant inverse directions of gene-pair correlations were noted in OP-MG versus controls OOM networks (r\u2009\u2265\u20090.92,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) involving most OP-MG genes overlapping prominently with muscle atrophy\/contractility and oxidative metabolism genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The gene expression in orbital muscles derived from OP-MG individuals compared with normal controls, support the pathogenic hypothesis previously generated from whole genome sequence analyses. Repression of gene transcripts in OP-MG orbital muscle implicate tissue-specific regulatory mechanisms, which may inform future biomarker discovery approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-020-01629-9","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T07:18:49Z","timestamp":1607671129000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gene expression profiling of orbital muscles in treatment-resistant ophthalmoplegic myasthenia gravis"],"prefix":"10.1186","volume":"15","author":[{"given":"Tarin A.","family":"Europa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Nel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-718X","authenticated-orcid":false,"given":"Jeannine M.","family":"Heckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"1629_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/nyas.13471","volume":"1412","author":"JM Heckmann","year":"2018","unstructured":"Heckmann JM, Nel M. A unique subphenotype of myasthenia gravis. Ann N Y Acad Sci. 2018;1412:14\u201320.","journal-title":"Ann N Y Acad Sci"},{"key":"1629_CR2","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.nmd.2007.07.002","volume":"17","author":"JM Heckmann","year":"2007","unstructured":"Heckmann JM, Owen EP, Little F. Myasthenia gravis in South Africans: racial differences in clinical manifestations. Neuromuscul Disord. 2007;17:929\u201334.","journal-title":"Neuromuscul Disord"},{"key":"1629_CR3","doi-asserted-by":"publisher","first-page":"532","DOI":"10.7196\/SAMJ.5390","volume":"102","author":"JM Heckmann","year":"2012","unstructured":"Heckmann JM, Hansen P, Van Toorn R, Lubbe E, Janse van Rensburg E, Wilmshurst JM. The characteristics of juvenile myasthenia gravis among South Africans. S Afr Med J. 2012;102:532\u20136.","journal-title":"S Afr Med J"},{"key":"1629_CR4","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1002\/mus.26172","volume":"58","author":"TA Europa","year":"2018","unstructured":"Europa TA, Nel M, Heckmann JM. Myasthenic ophthalmoparesis: time to resolution after initiating immune therapies. Muscle Nerve. 2018;58:542\u20139.","journal-title":"Muscle Nerve"},{"key":"1629_CR5","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.nmd.2017.06.009","volume":"27","author":"M Nel","year":"2017","unstructured":"Nel M, Jalali Sefid Dashti M, Gamieldien J, Heckmann JM. Exome sequencing identifies targets in the treatment-resistant ophthalmoplegic subphenotype of myasthenia gravis. Neuromuscul Disord. 2017;27:816\u201325.","journal-title":"Neuromuscul Disord"},{"key":"1629_CR6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3389\/fgene.2019.00136","volume":"10","author":"M Nel","year":"2019","unstructured":"Nel M, Mulder N, Europa TA, Heckmann JM. Using whole genome sequencing in an African subphenotype of myasthenia gravis to generate a pathogenetic hypothesis. Front Genet. 2019;10:136.","journal-title":"Front Genet"},{"key":"1629_CR7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13023-019-1003-y","volume":"14","author":"M Nel","year":"2019","unstructured":"Nel M, Prince S, Heckmann JM. Profiling of patient-specific myocytes identifies altered gene expression in the ophthalmoplegic subphenotype of myasthenia gravis. Orphanet J Rare Dis. 2019;14:24.","journal-title":"Orphanet J Rare Dis"},{"key":"1629_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature11632","volume":"491","author":"GR Abecasis","year":"2012","unstructured":"Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491:56\u201365.","journal-title":"Nature"},{"key":"1629_CR9","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1152\/physiolgenomics.00158.2004","volume":"22","author":"MD Fischer","year":"2005","unstructured":"Fischer MD, Budak MT, Bakay M, Gorospe JR, Kjellgren D, Pedrosa-Domellof F, Hoffman EP, Khurana TS. Definition of the unique human extraocular muscle allotype by expression profiling. Physiol Genom. 2005;22:283\u201391.","journal-title":"Physiol Genom"},{"key":"1629_CR10","doi-asserted-by":"publisher","first-page":"12062","DOI":"10.1073\/pnas.211257298","volume":"98","author":"JD Porter","year":"2001","unstructured":"Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, Leahy P, Li J, Andrade FH. Extraocular muscle is defined by a fundamentally distinct gene expression profile. Proc Natl Acad Sci U S A. 2001;98:12062\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1629_CR11","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1152\/physiolgenomics.00234.2004","volume":"24","author":"JD Porter","year":"2006","unstructured":"Porter JD, Israel S, Gong B, Merriam AP, Feuerman J, Khanna S, Kaminski HJ. Distinctive morphological and gene\/protein expression signatures during myogenesis in novel cell lines from extraocular and hindlimb muscle. Physiol Genom. 2006;24:264\u201375.","journal-title":"Physiol Genom"},{"key":"1629_CR12","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s40135-017-0141-4","volume":"5","author":"M Verma","year":"2017","unstructured":"Verma M, Fitzpatrick K, McLoon LK. Extraocular muscle repair and regeneration. Curr Ophthalmol Rep. 2017;5:207\u201315.","journal-title":"Curr Ophthalmol Rep"},{"key":"1629_CR13","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s10735-007-9085-6","volume":"38","author":"NC Cheng","year":"2007","unstructured":"Cheng NC, Liao SL, Wang IJ, Lin IC, Tang YB. Fiber type and myosin heavy chain compositions of adult pretarsal orbicularis oculi muscle. J Mol Histol. 2007;38:177\u201382.","journal-title":"J Mol Histol"},{"key":"1629_CR14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1212\/WNL.46.1.30","volume":"46","author":"JD Porter","year":"1996","unstructured":"Porter JD, Baker RS. Muscles of a different \u201ccolor\u201d: the unusual properties of the extraocular muscles may predispose or protect them in neurogenic and myogenic disease. Neurology. 1996;46:30\u20137.","journal-title":"Neurology"},{"key":"1629_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1098-2353(1999)12:1<1::AID-CA1>3.0.CO;2-J","volume":"12","author":"CW Goodmurphy","year":"1999","unstructured":"Goodmurphy CW, Ovalle WK. Morphological study of two human facial muscles: orbicularis oculi and corrugator supercilii. Clin Anat. 1999;12:1\u201311.","journal-title":"Clin Anat"},{"key":"1629_CR16","doi-asserted-by":"publisher","first-page":"30196438","DOI":"10.1371\/journal.pone.0196438","volume":"13","author":"J Kuang","year":"2018","unstructured":"Kuang J, Yan X, Genders AJ, Granata C, Bishop DJ. An overview of technical considerations when using quantitative real-time PCR analysis of gene expression in human exercise research. PLoS ONE. 2018;13:30196438. https:\/\/doi.org\/10.1371\/journal.pone.0196438.","journal-title":"PLoS ONE"},{"key":"1629_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-014-0179-6","volume":"3","author":"M Maurer","year":"2015","unstructured":"Maurer M, Bougoin S, Feferman T, Frenkian M, Bismuth J, Mouly V, et al. IL-6 and Akt are involved in muscular pathogenesis in myasthenia gravis. Acta Neuropathol Commun. 2015;3:1.","journal-title":"Acta Neuropathol Commun"},{"key":"1629_CR18","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3389\/fphys.2016.00524","volume":"7","author":"HJ Kaminski","year":"2016","unstructured":"Kaminski HJ, Himuro K, Alshaikh J, Gong B, Cheng G, Kusner LL. Differential RNA expression profile of skeletal muscle induced by experimental autoimmune myasthenia gravis in rats. Front Physiol. 2016;7:524.","journal-title":"Front Physiol"},{"key":"1629_CR19","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1097\/WNO.0000000000000534","volume":"37","author":"RM Rautenbach","year":"2017","unstructured":"Rautenbach RM, Pillay K, Murray ADN, Heckmann JM. Extraocular muscle findings in myasthenia gravis associated treatment-resistant ophthalmoplegia. J Neuroophthalmol. 2017;37:414\u20137.","journal-title":"J Neuroophthalmol"},{"key":"1629_CR20","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s00424-005-0010-0","volume":"452","author":"FH Andrade","year":"2006","unstructured":"Andrade FH, McMullen CA. Lactate is a metabolic substrate that sustains extraocular muscle function. Pflugers Arch. 2006;452:102\u20138.","journal-title":"Pflugers Arch"},{"key":"1629_CR21","doi-asserted-by":"publisher","first-page":"5168","DOI":"10.1167\/iovs.12-9785","volume":"53","author":"AL Altick","year":"2012","unstructured":"Altick AL, Feng CY, Schlauch K, Johnson LA, von Bartheld CS. Differences in gene expression between strabismic and normal human extraocular muscles. Investig Ophthalmol Vis Sci. 2012;53:5168\u201377.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1629_CR22","doi-asserted-by":"publisher","first-page":"5576","DOI":"10.1167\/iovs.16-20294","volume":"57","author":"AB Agarwal","year":"2016","unstructured":"Agarwal AB, Feng CY, Altick AL, Quilici DR, Wen D, Johnson LA, von Bartheld CS. Altered protein composition and gene expression in strabismic human extraocular muscles and tendons. Investig Ophthalmol Vis Sci. 2016;57:5576\u201385.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1629_CR23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1152\/physiolgenomics.00115.2001","volume":"9","author":"MD Fischer","year":"2002","unstructured":"Fischer MD, Gorospe JR, Felder E, Bogdanovich S, Pedrosa-Domellof F, Ahima RS, Rubinstein NA, Hoffman EP, Khurana TS. Expression profiling reveals metabolic and structural components of extraocular muscles. Physiol Genom. 2002;9:71\u201384.","journal-title":"Physiol Genom"},{"key":"1629_CR24","doi-asserted-by":"publisher","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3:RESEARCH0034.","journal-title":"Genome Biol"},{"key":"1629_CR25","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","volume":"26","author":"MW Pfaffl","year":"2004","unstructured":"Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper\u2013Excel-based tool using pair-wise correlations. Biotechnol Lett. 2004;26:509\u201315.","journal-title":"Biotechnol Lett"},{"key":"1629_CR26","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101\u20138.","journal-title":"Nat Protoc"},{"key":"1629_CR27","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.gene.2012.11.028","volume":"518","author":"A Fukushima","year":"2013","unstructured":"Fukushima A. DiffCorr: an R package to analyze and visualize differential correlations in biological networks. Gene. 2013;518:209\u201314.","journal-title":"Gene"},{"key":"1629_CR28","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/mus.23240","volume":"45","author":"KA Park","year":"2012","unstructured":"Park KA, Lim J, Sohn S, Oh SY. Myosin heavy chain isoform expression in human extraocular muscles: longitudinal variation and patterns of expression in global and orbital layers. Muscle Nerve. 2012;45:713\u201320.","journal-title":"Muscle Nerve"},{"key":"1629_CR29","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1074\/jbc.M112.429647","volume":"288","author":"N Stupka","year":"2013","unstructured":"Stupka N, Kintakas C, White JD, Fraser FW, Hanciu M, Aramaki-Hattori N, et al. Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion. J Biol Chem. 2013;288:1907\u201317.","journal-title":"J Biol Chem"},{"key":"1629_CR30","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.nmd.2008.08.005","volume":"18","author":"JS Beckmann","year":"2008","unstructured":"Beckmann JS, Spencer M. Calpain 3, the \u201cgatekeeper\u201d of proper sarcomere assembly, turnover and maintenance. Neuromuscul Disord. 2008;18:913\u201321.","journal-title":"Neuromuscul Disord"},{"key":"1629_CR31","doi-asserted-by":"publisher","first-page":"4542","DOI":"10.1128\/MCB.23.13.4542-4558.2003","volume":"23","author":"P Coulombe","year":"2003","unstructured":"Coulombe P, Rodier G, Pelletier S, Pellerin J, Meloche S. Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation. Mol Cell Biol. 2003;23:4542\u201358.","journal-title":"Mol Cell Biol"},{"key":"1629_CR32","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.imr.2014.09.001","volume":"3","author":"LD Tryon","year":"2014","unstructured":"Tryon LD, Vainshtein A, Memme JM, Crilly MJ, Hood DA. Recent advances in mitochondrial turnover during chronic muscle disuse. Integr Med Res. 2014;3:161\u201371.","journal-title":"Integr Med Res"},{"key":"1629_CR33","first-page":"575","volume":"19","author":"S van Dam","year":"2018","unstructured":"van Dam S, Vosa U, van der Graaf A, Franke L, de Magalhaes JP. Gene co-expression analysis for functional classification and gene-disease predictions. Brief Bioinform. 2018;19:575\u201392.","journal-title":"Brief Bioinform"},{"key":"1629_CR34","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1016\/j.celrep.2014.05.010","volume":"7","author":"E Dardenne","year":"2014","unstructured":"Dardenne E, Polay Espinoza M, Fattet L, Germann S, Lambert MP, Neil H, et al. RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation. Cell Rep. 2014;7:1900\u201313.","journal-title":"Cell Rep"},{"key":"1629_CR35","doi-asserted-by":"publisher","first-page":"28925","DOI":"10.1074\/jbc.272.46.28925","volume":"272","author":"W Chang","year":"1997","unstructured":"Chang W, Gelman MS, Prives JM. Calnexin-dependent enhancement of nicotinic acetylcholine receptor assembly and surface expression. J Biol Chem. 1997;272:28925\u201332.","journal-title":"J Biol Chem"},{"key":"1629_CR36","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1083\/jcb.201806191","volume":"218","author":"L Wang","year":"2019","unstructured":"Wang L, Yan Z, Vihinen H, Eriksson O, Wang W, Soliymani R, et al. FAM92A1 is a BAR domain protein required for mitochondrial ultrastructure and function. J Cell Biol. 2019;218:97\u2013111.","journal-title":"J Cell Biol"},{"key":"1629_CR37","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.cell.2016.09.026","volume":"167","author":"CA McGourty","year":"2016","unstructured":"McGourty CA, Akopian D, Walsh C, Gorur A, Werner A, Schekman R, et al. Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co-adaptor. Cell. 2016;167:525\u201338.","journal-title":"Cell"},{"key":"1629_CR38","doi-asserted-by":"publisher","first-page":"D296","DOI":"10.1093\/nar\/gkx1067","volume":"46","author":"CH Chou","year":"2018","unstructured":"Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46:D296-302.","journal-title":"Nucleic Acids Res"},{"key":"1629_CR39","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1152\/physiolgenomics.00169.2009","volume":"41","author":"U Zeiger","year":"2010","unstructured":"Zeiger U, Khurana TS. Distinctive patterns of microRNA expression in extraocular muscles. Physiol Genom. 2010;41:289\u201396.","journal-title":"Physiol Genom"},{"key":"1629_CR40","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1007\/s12035-013-8540-5","volume":"49","author":"P Cisternas","year":"2014","unstructured":"Cisternas P, Henriquez JP, Brandan E, Inestrosa NC. Wnt signaling in skeletal muscle dynamics: myogenesis, neuromuscular synapse and fibrosis. Mol Neurobiol. 2014;49:574\u201389.","journal-title":"Mol Neurobiol"},{"key":"1629_CR41","doi-asserted-by":"publisher","first-page":"e00305","DOI":"10.1128\/MCB.00305-16","volume":"37","author":"S Summermatter","year":"2017","unstructured":"Summermatter S, Bouzan A, Pierrel E, Melly S, Stauffer D, Gutzwiller S, et al. Blockade of metallothioneins 1 and 2 increases skeletal muscle mass and strength. Mol Cell Biol. 2017;37:e00305-e316.","journal-title":"Mol Cell Biol"},{"key":"1629_CR42","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.1111\/febs.12338","volume":"280","author":"P Munoz-Canoves","year":"2013","unstructured":"Munoz-Canoves P, Scheele C, Pedersen BK, Serrano AL. Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? Febs J. 2013;280:4131\u201348.","journal-title":"Febs J"},{"key":"1629_CR43","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"Consortium GT","year":"2013","unstructured":"Consortium GT. The genotype-tissue expression (GTEx) project. Nat Genet. 2013;45:580\u20135.","journal-title":"Nat Genet"},{"key":"1629_CR44","doi-asserted-by":"publisher","first-page":"11230","DOI":"10.1038\/s41598-020-68185-x","volume":"10","author":"Y Hong","year":"2020","unstructured":"Hong Y, Liang X, Gilhus NE. AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study. Sci Rep. 2020;10:11230.","journal-title":"Sci Rep"},{"key":"1629_CR45","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.nmd.2019.03.009","volume":"29","author":"TA Europa","year":"2019","unstructured":"Europa TA, Nel M, Heckmann JM. A review of the histopathological findings in myasthenia gravis: clues to the pathogenesis of treatment-resistance in extraocular muscles. Neuromuscul Disord. 2019;29:381\u20137.","journal-title":"Neuromuscul Disord"},{"key":"1629_CR46","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tem.2014.06.002","volume":"25","author":"R Sartori","year":"2014","unstructured":"Sartori R, Gregorevic P, Sandri M. TGFbeta and BMP signaling in skeletal muscle: potential significance for muscle-related disease. Trends Endocrinol Metab. 2014;25:464\u201371.","journal-title":"Trends Endocrinol Metab"},{"key":"1629_CR47","first-page":"267","volume":"346","author":"DJ Glass","year":"2010","unstructured":"Glass DJ. PI3 kinase regulation of skeletal muscle hypertrophy and atrophy. Curr Top Microbiol Immunol. 2010;346:267\u201378.","journal-title":"Curr Top Microbiol Immunol"},{"key":"1629_CR48","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.nmd.2014.02.010","volume":"24","author":"J Auret","year":"2014","unstructured":"Auret J, Abrahams A, Prince S, Heckmann JM. The effects of prednisone and steroid-sparing agents on decay accelerating factor (CD55) expression: implications in myasthenia gravis. Neuromuscul Disord. 2014;24:499\u2013508.","journal-title":"Neuromuscul Disord"},{"key":"1629_CR49","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/jhg.2015.146","volume":"61","author":"M Nel","year":"2016","unstructured":"Nel M, Buys JM, Rautenbach R, Mowla S, Prince S, Heckmann JM. The African-387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis. J Hum Genet. 2016;61:307\u201316.","journal-title":"J Hum Genet"},{"key":"1629_CR50","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1167\/iovs.02-0673","volume":"44","author":"LK McLoon","year":"2003","unstructured":"McLoon LK, Wirtschafter J. Activated satellite cells in extraocular muscles of normal adult monkeys and humans. Investig Ophthalmol Vis Sci. 2003;44:1927\u201332.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1629_CR51","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1167\/iovs.07-0600","volume":"49","author":"BC Anderson","year":"2008","unstructured":"Anderson BC, Christiansen SP, McLoon LK. Myogenic growth factors can decrease extraocular muscle force generation: a potential biological approach to the treatment of strabismus. Investig Ophthalmol Vis Sci. 2008;49:221\u20139.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1629_CR52","doi-asserted-by":"publisher","first-page":"5482","DOI":"10.1167\/iovs.14-14886","volume":"55","author":"LK McLoon","year":"2014","unstructured":"McLoon LK, Harandi VM, Brannstrom T, Andersen PM, Liu JX. Wnt and extraocular muscle sparing in amyotrophic lateral sclerosis. Investig Ophthalmol Vis Sci. 2014;55:5482\u201396.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1629_CR53","doi-asserted-by":"publisher","first-page":"4348","DOI":"10.1167\/iovs.14-14422","volume":"55","author":"Y Zhou","year":"2014","unstructured":"Zhou Y, Kaminski HJ, Gong B, Cheng G, Feuerman JM, Kusner L. RNA expression analysis of passive transfer myasthenia supports extraocular muscle as a unique immunological environment. Invest Ophthalmol Vis Sci. 2014;55:4348\u201359.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1629_CR54","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1085\/jgp.201511542","volume":"147","author":"M Sekulic-Jablanovic","year":"2016","unstructured":"Sekulic-Jablanovic M, Ullrich ND, Goldblum D, Palmowski-Wolfe A, Zorzato F, Treves S. Functional characterization of orbicularis oculi and extraocular muscles. J Gen Physiol. 2016;147:395\u2013406.","journal-title":"J Gen Physiol"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-020-01629-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-020-01629-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-020-01629-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T07:28:04Z","timestamp":1607671684000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-020-01629-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1629"],"URL":"https:\/\/doi.org\/10.1186\/s13023-020-01629-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-64758\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-64758\/v1","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"25 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 257\/2012) and all participants provided informed written consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All persons participating in this study agreed to their anonymous data being published and shared.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"346"}}