{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:57:53Z","timestamp":1787162273082,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Myofibrillar myopathy is a group of hereditary neuromuscular disorders characterized by dissolution of myofibrils and abnormal intracellular accumulation of Z disc-related proteins. We aimed to characterize the clinical, physiological, pathohistological, and genetic features of Chinese myofibrillar myopathy patients from a single neuromuscular center.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    A total of 18 patients were enrolled. Demographic and clinical data were collected. Laboratory investigations, electromyography, and cardiac evaluation was performed. Routine and immunohistochemistry stainings against desmin, \u03b1B-crystallin, and BAG3 of muscle specimen were carried out. Finally, next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders were performed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Twelve pathogenic variants in\n                    <jats:italic>DES, BAG3, FLNC, FHL1<\/jats:italic>\n                    , and\n                    <jats:italic>TTN<\/jats:italic>\n                    were identified, of which seven were novel mutations. The novel\n                    <jats:italic>DES<\/jats:italic>\n                    c.1256C&amp;gt;T substitution is a high frequency mutation. The combined recessively\/dominantly transmitted c.19993G&amp;gt;T and c.107545delG mutations in\n                    <jats:italic>TTN<\/jats:italic>\n                    gene cause a limb girdle muscular dystrophy phenotype with the classical myofibrillar myopathy histological changes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    We report for the first time that hereditary myopathy with early respiratory failure patient can have peripheral nerve and severe spine involvement. The mutation in Ig-like domain 16 of\n                    <jats:italic>FLNC<\/jats:italic>\n                    is associated with the limb girdle type of filaminopathy, and the mutation in Ig-like domain 18 with distal myopathy type. These findings expand the phenotypic and genotypic correlation spectrum of myofibrillar myopathy.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2020.01014","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:48:35Z","timestamp":1600130915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Expanding the Clinico-Genetic Spectrum of Myofibrillar Myopathy: Experience From a Chinese Neuromuscular Center"],"prefix":"10.3389","volume":"11","author":[{"given":"Yue-Bei","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqian","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1097\/WCO.0000000000000357","article-title":"New aspects of myofibrillar myopathies","volume":"29","author":"Kley","year":"2016","journal-title":"Curr Opin Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"E124","DOI":"10.1002\/mus.26036","article-title":"Myofibrillar myopathy due to dominant LMNA mutations: a report of 2 cases","volume":"57","author":"Dhawan","year":"2018","journal-title":"Muscle Nerve."},{"key":"B3","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1212\/WNL.0000000000002324","article-title":"Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy","volume":"86","author":"Ghaoui","year":"2016","journal-title":"Neurology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.nmd.2015.04.002","article-title":"Severe congenital actin related myopathy with myofibrillar myopathy features","volume":"25","author":"Selcen","year":"2015","journal-title":"Neuromuscul Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1038\/ng.1103","article-title":"Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy","volume":"44","author":"Sarparanta","year":"2012","journal-title":"Nat Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1097\/01.cnd.0000159779.32828.e7","article-title":"Epidermolysis bullosa simplex associated with muscular dystrophy and cardiac involvement","volume":"6","author":"Celik","year":"2005","journal-title":"J Clin Neuromuscul Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1001\/jamaneurol.2017.4899","article-title":"Interpreting genetic variants in titin in patients with muscle disorders","volume":"75","author":"Savarese","year":"2018","journal-title":"JAMA Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1093\/brain\/awn325","article-title":"Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1","volume":"132","author":"Schessl","year":"2009","journal-title":"Brain."},{"key":"B9","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/ana.24102","article-title":"Atypical phenotypes in titinopathies explained by second titin mutations","volume":"75","author":"Evila","year":"2014","journal-title":"Ann Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e825","DOI":"10.1002\/mgg3.825","article-title":"A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family","volume":"7","author":"Ma","year":"2019","journal-title":"Mol Genet Genomic Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1097\/CM9.0000000000000001","article-title":"A novel phenotype with splicing mutation identified in a Chinese family with desminopathy","volume":"132","author":"Fan","year":"2019","journal-title":"Chin Med J (Engl)."},{"key":"B12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12883-018-1078-4","article-title":"A case report: a heterozygous deletion (2791_2805 del) in exon 18 of the filamin C gene causing filamin C-related myofibrillar myopathies in a Chinese family","volume":"18","author":"Miao","year":"2018","journal-title":"BMC Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1111\/cge.13715","article-title":"Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese","volume":"97","author":"Lee","year":"2020","journal-title":"Clin Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1007\/s00439-003-1057-7","article-title":"Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy","volume":"114","author":"Kaminska","year":"2004","journal-title":"Hum Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/ana.21553","article-title":"Mutation in BAG3 causes severe dominant childhood muscular dystrophy","volume":"65","author":"Selcen","year":"2009","journal-title":"Ann Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1093\/brain\/aws103","article-title":"Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin","volume":"135","author":"Ohlsson","year":"2012","journal-title":"Brain."},{"key":"B17","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1136\/jnnp-2014-309009","article-title":"Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure","volume":"86","author":"Uruha","year":"2015","journal-title":"J Neurolo Neurosurg Psychiatry."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1093\/brain\/aws102","article-title":"Titin mutation segregates with hereditary myopathy with early respiratory failure","volume":"135","author":"Pfeffer","year":"2012","journal-title":"Brain."},{"key":"B19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.nmd.2014.11.005","article-title":"New disease allele and de novo mutation indicate mutational vulnerability of titin exon 343 in hereditary myopathy with early respiratory failure","volume":"25","author":"Yue","year":"2015","journal-title":"Neuromuscul Disord."},{"key":"B20","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1136\/jnnp-2012-304728","article-title":"Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure","volume":"85","author":"Pfeffer","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B21","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1007\/s00415-019-09187-2","article-title":"Expanding the importance of HMERF titinopathy: new mutations and clinical aspects","volume":"266","author":"Palmio","year":"2019","journal-title":"J Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1471-2377-13-29","article-title":"Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins","volume":"13","author":"Toro","year":"2013","journal-title":"BMC Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1136\/jnnp-2013-304965","article-title":"Hereditary myopathy with early respiratory failure: occurrence in various populations","volume":"85","author":"Palmio","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B24","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/j.1399-0004.2011.01659.x","article-title":"BAG3-related myofibrillar myopathy in a Chinese family","volume":"81","author":"Lee","year":"2012","journal-title":"Clin Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"13615","DOI":"10.1074\/jbc.M114.550418","article-title":"Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP) mutations in the actin-binding domain cause disruption of skeletal muscle actin filaments in myofibrillar myopathy","volume":"289","author":"Lin","year":"2014","journal-title":"J Biol Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/hmg\/ddg020","article-title":"Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly","volume":"12","author":"Salmikangas","year":"2003","journal-title":"Hum Mol Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3870","DOI":"10.1172\/JCI34472","article-title":"An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice","volume":"118","author":"Sheikh","year":"2008","journal-title":"J Clin Invest."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1006880","DOI":"10.1371\/journal.pgen.1006880","article-title":"Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion","volume":"13","author":"Gonzalez-Morales","year":"2017","journal-title":"PLoS Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"5879","DOI":"10.1093\/hmg\/ddu310","article-title":"Disruption of both nesprin 1 and desmin results in nuclear anchorage defects and fibrosis in skeletal muscle","volume":"23","author":"Chapman","year":"2014","journal-title":"Hum Mol Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7917","DOI":"10.1074\/jbc.M307473200","article-title":"Association of the chaperone \u03b1B-crystallin with titin in heart muscle","volume":"279","author":"Bullard","year":"2004","journal-title":"J Biol Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1002\/jnr.21231","article-title":"Structure, function, property, and role in neurologic diseases and other diseases of the sHsp22","volume":"85","author":"Hu","year":"2007","journal-title":"J Neurosci Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s12192-017-0788-7","article-title":"\u03b1B-crystallin is a sensor for assembly intermediates and for the subunit topology of desmin intermediate filaments","volume":"22","author":"Sharma","year":"2017","journal-title":"Cell Stress Chaperone."},{"key":"B33","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/embor.2010.203","article-title":"BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins","volume":"12","author":"Gamerdinger","year":"2011","journal-title":"EMBO Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4161\/auto.5.3.7894","article-title":"The stress-inducible HspB8-Bag3 complex induces the eIF2\u03b1 kinase pathway: implications for protein quality control and viral factory degradation?","volume":"5","author":"Carra","year":"2009","journal-title":"Autophagy."},{"key":"B35","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.ejcb.2018.03.003","article-title":"Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases","volume":"97","author":"Li","year":"2018","journal-title":"Eur J Cell Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e16828","DOI":"10.1371\/journal.pone.0016828","article-title":"BAG3 directly interacts with mutated \u03b1B-crystallin to suppress its aggregation and toxicity","volume":"6","author":"Hishiya","year":"2011","journal-title":"PLoS One."},{"key":"B37","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1002\/mus.25631","article-title":"Rigid spine syndrome associated with sensory-motor axonal neuropathy resembling Charcot-Marie-Tooth disease is characteristic of Bcl-2-associated athanogene-3 gene mutations even without cardiac involvement","volume":"57","author":"Noury","year":"2018","journal-title":"Muscle Nerve."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s13258-018-0721-1","article-title":"BAG3 mutation in a patient with atypical phenotypes of myofibrillar myopathy and Charcot-Marie-Tooth disease","volume":"40","author":"Kim","year":"2018","journal-title":"Genes Genomics."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5097","DOI":"10.1007\/s12035-015-9439-0","article-title":"Identification of a novel mutation in the titin gene in a Chinese family with limb-girdle muscular dystrophy 2J","volume":"53","author":"Zheng","year":"2016","journal-title":"Mol Neurobiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1002\/ana.25241","article-title":"Congenital titinopathy: comprehensive characterization and pathogenic insights","volume":"83","author":"Oates","year":"2018","journal-title":"Ann Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1212\/WNL.0b013e3182a6ca62","article-title":"Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy","volume":"81","author":"Ceyhan-Birsoy","year":"2013","journal-title":"Neurology."},{"key":"B42","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.nmd.2018.05.007","article-title":"229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017","volume":"28","author":"Straub","year":"2018","journal-title":"Neuromuscul Disord."},{"key":"B43","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.nmd.2017.12.002","article-title":"Hereditary myopathy with early respiratory failure (HMERF): Still rare, but common enough","volume":"28","author":"Tasca","year":"2018","journal-title":"Neuromuscul Disord."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1212\/WNL.0000000000002200","article-title":"A new titinopathy: childhood-juvenile onset Emery-Dreifuss-like phenotype without cardiomyopathy","volume":"85","author":"De Cid","year":"2015","journal-title":"Neurology."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1212\/WNL.0b013e31823dc51e","article-title":"Distal myopathy with upper limb predominance caused by filamin C haploinsufficiency","volume":"77","author":"Guergueltcheva","year":"2011","journal-title":"Neurology."},{"key":"B46","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.ajhg.2011.04.021","article-title":"Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy","volume":"88","author":"Duff","year":"2011","journal-title":"Am J Hum Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0186642","DOI":"10.1371\/journal.pone.0186642","article-title":"A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy","volume":"12","author":"Rossi","year":"2017","journal-title":"PLoS One."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1093\/brain\/awm271","article-title":"Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients","volume":"130","author":"Kley","year":"2007","journal-title":"Brain."},{"key":"B49","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/mus.23349","article-title":"Novel FLNC mutation in a patient with myofibrillar myopathy in combination with late-onset cerebellar ataxia","volume":"46","author":"Tasca","year":"2012","journal-title":"Muscle Nerve."},{"key":"B50","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/ejhg.2008.226","article-title":"In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy","volume":"17","author":"Shatunov","year":"2009","journal-title":"Eur J Hum Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1002\/humu.23559","article-title":"De novo mutations in FLNC leading to early-onset restrictive cardiomyopathy and congenital myopathy","volume":"39","author":"Kiselev","year":"2018","journal-title":"Hum Mutat."}],"updated-by":[{"DOI":"10.3389\/fneur.2020.636981","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000}}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.01014\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T04:34:44Z","timestamp":1610253284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.01014\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,15]]},"references-count":51,"alternative-id":["10.3389\/fneur.2020.01014"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2020.01014","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,15]]},"article-number":"1014"}}