{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:11:43Z","timestamp":1767204703073,"version":"build-2238731810"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800219"],"award-info":[{"award-number":["81800219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873686"],"award-info":[{"award-number":["81873686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2019JJ50927"],"award-info":[{"award-number":["2019JJ50927"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2020JJ3057"],"award-info":[{"award-number":["2020JJ3057"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2020JJ4830"],"award-info":[{"award-number":["2020JJ4830"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Limb-girdle muscular dystrophies (LGMD) are hereditary genetic disorders characterized by progressive muscle impairment which predominantly include proximal muscle weaknesses in the pelvic and shoulder girdles. This article describes an attempt to identify genetic cause(s) for a LGMD pedigree via a combination of whole exome sequencing and Sanger sequencing. Digenic variants, the titin gene (\n                    <jats:italic>TTN<\/jats:italic>\n                    ) c.19481T&amp;gt;G (p.Leu6494Arg) and the trafficking protein particle complex 11 gene (\n                    <jats:italic>TRAPPC11<\/jats:italic>\n                    ) c.3092C&amp;gt;G (p.Pro1031Arg), co-segregated with the disease phenotype in the family, suggesting their possible pathogenicity.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2021.601757","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T01:11:16Z","timestamp":1614820276000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Digenic Variants in the TTN and TRAPPC11 Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family"],"prefix":"10.3389","volume":"15","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"207","DOI":"10.36185\/2532-1900-024","article-title":"LGMD. Identification, description and classification.","volume":"39","author":"Angelini","year":"2020","journal-title":"Acta Myol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1515\/rjim-2015-0002","article-title":"The growing family of limb-girdle muscular dystrophies: old and newly identified members.","volume":"53","author":"Bastian","year":"2015","journal-title":"Rom. J. Intern. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ajhg.2013.05.028","article-title":"Recessive TRAPPC11 mutations cause a disease spectrum of limb girdle muscular dystrophy and myopathy with movement disorder and intellectual disability.","volume":"93","author":"B\u00f6gershausen","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1085\/jgp.201311129","article-title":"Removal of immunoglobulin-like domains from titin\u2019s spring segment alters titin splicing in mouse skeletal muscle and causes myopathy.","volume":"143","author":"Buck","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.559327","article-title":"Clinical and genomic evaluation of 207 genetic myopathies in the Indian subcontinent.","volume":"11","author":"Chakravorty","year":"2020","journal-title":"Front. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4608","DOI":"10.1093\/hmg\/ddq388","article-title":"Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies.","volume":"19","author":"Charton","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1002\/humu.22611","article-title":"A rising titan: TTN review and mutation update.","volume":"35","author":"Chauveau","year":"2014","journal-title":"Hum. Mutat."},{"key":"B8","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1590\/0004-282x20140110","article-title":"Common recessive limb-girdle muscular dystrophies differential diagnosis: why and how?","volume":"72","author":"Cotta","year":"2014","journal-title":"Arq. Neuropsiquiatr."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1091\/mbc.E15-08-0557","article-title":"Trappc11 is required for protein glycosylation in zebrafish and humans.","volume":"27","author":"DeRossi","year":"2016","journal-title":"Mol. Biol. Cell."},{"key":"B10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s12551-017-0269-3","article-title":"An historical perspective of the discovery of titin filaments.","volume":"9","author":"Dos Remedios","year":"2017","journal-title":"Biophys. Rev."},{"key":"B11","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":"Evil\u00e4","year":"2014","journal-title":"Ann. Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/CND.0000000000000173","article-title":"Siblings with mutations in TRAPPC11 presenting with limb-girdle muscular dystrophy 2S.","volume":"19","author":"Fee","year":"2017","journal-title":"J. Clin. Neuromusc. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"W60","DOI":"10.1093\/nar\/gky311","article-title":"GeneMANIA update 2018.","volume":"46","author":"Franz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"D900","DOI":"10.1093\/nar\/gkv1068","article-title":"DIDA: a curated and annotated digenic diseases database.","volume":"44","author":"Gazzo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2016.00021","article-title":"A review of the giant protein titin in clinical molecular diagnositics of cardiomyopathies.","volume":"3","author":"Gigli","year":"2016","journal-title":"Front. Cardiovasc. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1111\/jcmm.13068","article-title":"Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.","volume":"21","author":"Hu","year":"2017","journal-title":"J. Cell Mol. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1212\/con.0000000000000406","article-title":"The limb-girdle muscular dystrophies and the dystrophinopathies.","volume":"22","author":"Iyadurai","year":"2016","journal-title":"Continuum"},{"key":"B18","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s00424-019-02272-5","article-title":"Titin mutations and muscle disease.","volume":"471","author":"Kellermayer","year":"2019","journal-title":"Pflugers Arch."},{"key":"B19","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1136\/jmedgenet-2016-104108","article-title":"A novel TRAPPC11 mutation in two Turkish families associated with cerebral atrophy, global retardation, scoliosis, achalasia and alacrima.","volume":"54","author":"Koehler","year":"2017","journal-title":"J. Med. Genet."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-015-0056-4","article-title":"Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype.","volume":"5","author":"Liang","year":"2015","journal-title":"Skelet. Muscle"},{"key":"B21","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/mus.26077","article-title":"Untangling the complexity of limb-girdle muscular dystrophies.","volume":"58","author":"Liewluck","year":"2018","journal-title":"Muscle Nerve"},{"key":"B22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/mus.25192","article-title":"The Italian limb girdle muscular dystrophy registry: relative frequency, clinical features, and differential diagnosis.","volume":"55","author":"Magri","year":"2017","journal-title":"Muscle Nerve"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.3892\/mmr.2014.2048","article-title":"Limb-girdle muscular dystrophies: where next after six decades from the first proposal (review).","volume":"9","author":"Mahmood","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/humu.23145","article-title":"Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.","volume":"38","author":"Matalonga","year":"2017","journal-title":"Hum. Mutat."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1212\/wnl.0000000000000892","article-title":"Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practice issues review panel of the American Association of Neuromuscular & Electrodiagnostic Medicine.","volume":"83","author":"Narayanaswami","year":"2014","journal-title":"Neurology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s10741-015-9495-6","article-title":"Titin mutations: the fall of goliath.","volume":"20","author":"Neiva-Sousa","year":"2015","journal-title":"Heart Fail. Rev."},{"key":"B27","first-page":"1","article-title":"Genetic basis of limb-girdle muscular dystrophies: the 2014 update.","volume":"33","author":"Nigro","year":"2014","journal-title":"Acta Myol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1159\/000492664","article-title":"Limb girdle muscular dystrophy due to digenic inheritance of DES and CAPN3 mutations.","volume":"10","author":"Peddareddygari","year":"2018","journal-title":"Case Rep. Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3233\/jnd-160158","article-title":"Increasing role of titin mutations in neuromuscular disorders.","volume":"3","author":"Savarese","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1091\/mbc.E10-11-0873","article-title":"C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.","volume":"22","author":"Scrivens","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"B31","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":"B32","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/ejhg.2008.9","article-title":"Revised spectrum of mutations in sarcoglycanopathies.","volume":"16","author":"Trabelsi","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.mcp.2015.05.004","article-title":"Targeted 46-gene and clinical exome sequencing for mutations causing cardiomyopathies.","volume":"29","author":"Waldm\u00fcller","year":"2015","journal-title":"Mol. Cell. Probes"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8090797","article-title":"Novel TRAPPC11 mutations in a Chinese pedigree of limb girdle muscular dystrophy.","volume":"2018","author":"Wang","year":"2018","journal-title":"Case Rep. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/emboj.2009.350","article-title":"A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway.","volume":"29","author":"Wendler","year":"2010","journal-title":"EMBO. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/cge.13597","article-title":"Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy.","volume":"96","author":"Winckler","year":"2019","journal-title":"Clin. Genet."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175343","article-title":"Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing.","volume":"12","author":"Yu","year":"2017","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1097\/OPX.0000000000000518","article-title":"Identification of a novel GJA3 mutation in congenital nuclear cataract.","volume":"92","author":"Yuan","year":"2015","journal-title":"Optom. Vis. Sci."},{"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":"","journal-title":"Mol. Neurobiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s12035-014-9047-4","article-title":"Identification of a premature termination mutation in the proline-rich transmembrane protein 2 gene in a Chinese family with febrile seizures.","volume":"53","author":"Zheng","year":"","journal-title":"Mol. Neurobiol."}],"updated-by":[{"DOI":"10.3389\/fnins.2021.678618","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000}}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.601757\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T05:35:32Z","timestamp":1618896932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.601757\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":40,"alternative-id":["10.3389\/fnins.2021.601757"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2021.601757","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]},"article-number":"601757"}}