{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:23:58Z","timestamp":1784154238232,"version":"3.55.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1HG008900"],"award-info":[{"award-number":["UM1HG008900"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["779257"],"award-info":[{"award-number":["779257"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NFDI 1\/1"],"award-info":[{"award-number":["NFDI 1\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["441914366"],"award-info":[{"award-number":["441914366"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["461264291"],"award-info":[{"award-number":["461264291"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["305444"],"award-info":[{"award-number":["305444"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HG011755"],"award-info":[{"award-number":["U01HG011755"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HG009141"],"award-info":[{"award-number":["R01HG009141"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA577346\/18NM05"],"award-info":[{"award-number":["MDA577346\/18NM05"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","award":["18GRO-PG24\\u20130271"],"award-info":[{"award-number":["18GRO-PG24\\u20130271"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","nmd-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuromuscular Disorders"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.nmd.2025.105415","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T11:26:26Z","timestamp":1748949986000},"page":"105415","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Multi-omics approach identifies a novel recessive pathogenic variant in the TNNT3 gene in two siblings with congenital myopathy"],"prefix":"10.1016","volume":"52","author":[{"given":"Juliane S.","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Rabinowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Zaharieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Pini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente A.","family":"Y\u00e9pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Esteve-Codina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Herron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Healy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandya","family":"Tirupathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"T\u00f6pf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"DiTroia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Phadke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sarkozy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nmd.2025.105415_bib0001","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1152\/physrev.2000.80.2.853","article-title":"Regulation of contraction in striated muscle","volume":"80","author":"Gordon","year":"2000","journal-title":"Physiol Rev"},{"key":"10.1016\/j.nmd.2025.105415_bib0002","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-biochem-052521-042909","article-title":"Structural biochemistry of muscle contraction","volume":"92","author":"Wang","year":"2023","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.nmd.2025.105415_bib0003","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1016\/S0021-9258(18)62075-7","article-title":"Reconstitution of troponin activity from three protein components","volume":"246","author":"Greaser","year":"1971","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2025.105415_bib0004","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s00239-009-9202-0","article-title":"To investigate protein evolution by detecting suppressed epitope structures","volume":"68","author":"Chong","year":"2009","journal-title":"J Mol Evol"},{"key":"10.1016\/j.nmd.2025.105415_bib0005","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.abb.2010.10.013","article-title":"Troponin T isoforms and posttranscriptional modifications: evolution, regulation and function","volume":"505","author":"Wei","year":"2011","journal-title":"Arch Biochem Biophys"},{"key":"10.1016\/j.nmd.2025.105415_bib0006","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fphys.2014.00165","article-title":"Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review","volume":"5","author":"Sheng","year":"2014","journal-title":"Front Physiol"},{"key":"10.1016\/j.nmd.2025.105415_bib0007","first-page":"22","article-title":"Troponin variants in congenital myopathies: how they affect skeletal muscle mechanics","author":"van de Locht","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.nmd.2025.105415_bib0008","doi-asserted-by":"crossref","first-page":"eadg2841","DOI":"10.1126\/scitranslmed.adg2841","article-title":"Pathogenic TNNI1 variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease","volume":"16","author":"Donkervoort","year":"2024","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.nmd.2025.105415_bib0009","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1086\/376418","article-title":"Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B","volume":"73","author":"Sung","year":"2003","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0010","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000365057","article-title":"Exome sequencing identifies a dominant TNNT3 mutation in a large Family with distal arthrogryposis","volume":"5","author":"Daly","year":"2014","journal-title":"Mol Syndromol"},{"key":"10.1016\/j.nmd.2025.105415_bib0011","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/ajmg.a.35809","article-title":"Spectrum of mutations that cause distal arthrogryposis types 1 and 2B","volume":"161A","author":"Beck","year":"2013","journal-title":"Am J Med Genet A"},{"key":"10.1016\/j.nmd.2025.105415_bib0012","article-title":"Diagnostic work-up and phenotypic characteristics of a family with variable severity of distal arthrogryposis type 2B (Sheldon-Hall syndrome) and TNNT3 pathogenic variant","volume":"13","author":"Dabaj","year":"2022","journal-title":"Front Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0013","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ejmg.2011.03.002","article-title":"A novel mutation in TNNT3 associated with Sheldon-Hall syndrome in a Chinese family with vertical talus","volume":"54","author":"Zhao","year":"2011","journal-title":"Eur J Med Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0014","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/humu.23385","article-title":"Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant","volume":"39","author":"Sandaradura","year":"2018","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2025.105415_bib0015","doi-asserted-by":"crossref","first-page":"e589","DOI":"10.1212\/NXG.0000000000000589","article-title":"Biallelic pathogenic variants in TNNT3 associated with congenital myopathy","volume":"7","author":"Calame","year":"2021","journal-title":"Neurol Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0016","first-page":"717","article-title":"The RD-Connect genome-Phenome Analysis Platform: accelerating diagnosis, research, and gene discovery for rare diseases","volume":"43","author":"Laurie","year":"2022","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2025.105415_bib0017","series-title":"Muscle biopsy: A practical approach","author":"Dubowitz","year":"2021"},{"key":"10.1016\/j.nmd.2025.105415_bib0018","first-page":"25","article-title":"An integrated transcriptomics and genomics approach detects an X\/autosome translocation in a female with duchenne muscular dystrophy","author":"Segarra-Casas","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.nmd.2025.105415_bib0019","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41431-024-01699-4","article-title":"Phenotype-driven genomics enhance diagnosis in children with unresolved neuromuscular diseases","volume":"33","author":"Estevez-Arias","year":"2025","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0020","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1038\/s41596-020-00462-5","article-title":"Detection of aberrant gene expression events in RNA sequencing data","volume":"16","author":"Yepez","year":"2021","journal-title":"Nat Protoc"},{"key":"10.1016\/j.nmd.2025.105415_bib0021","doi-asserted-by":"crossref","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.nmd.2025.105415_bib0022","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.ajhg.2018.10.025","article-title":"OUTRIDER: a statistical method for detecting aberrantly expressed genes in RNA sequencing data","volume":"103","author":"Brechtmann","year":"2018","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0023","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.nmd.2025.105415_bib0024","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.ajhg.2023.10.014","article-title":"Improved detection of aberrant splicing with FRASER 2.0 and the intron jaccard index","volume":"110","author":"Scheller","year":"2023","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0025","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41467-020-20573-7","article-title":"Detection of aberrant splicing events in RNA-seq data using FRASER","volume":"12","author":"Mertes","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.nmd.2025.105415_bib0026","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1096\/fj.06-6899com","article-title":"Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that cause distal arthrogryposis all increase contractile function","volume":"21","author":"Robinson","year":"2007","journal-title":"FASEB J"},{"key":"10.1016\/j.nmd.2025.105415_bib0027","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1113\/expphysiol.2006.036525","article-title":"Plasticity of human skeletal muscle: gene expression to in vivo function","volume":"92","author":"Harridge","year":"2007","journal-title":"Exp Physiol"},{"key":"10.1016\/j.nmd.2025.105415_bib0028","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1002\/j.2040-4603.2013.tb00534.x","article-title":"Mechanisms modulating skeletal muscle phenotype","volume":"3","author":"Blaauw","year":"2013","journal-title":"Compr Physiol"},{"key":"10.1016\/j.nmd.2025.105415_bib0029","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1086\/303089","article-title":"A novel nemaline myopathy in the Amish caused by a mutation in troponin T1","volume":"67","author":"Johnston","year":"2000","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.nmd.2025.105415_bib0030","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/cfg.343","article-title":"Structure and sequence of the human fast skeletal troponin T (TNNT3) gene: insight into the evolution of the gene and the origin of the developmentally regulated isoforms","volume":"4","author":"Stefancsik","year":"2003","journal-title":"Comp Funct Genomics"},{"key":"10.1016\/j.nmd.2025.105415_bib0031","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0378-1119(97)00100-5","article-title":"Primary structure and developmental acidic to basic transition of 13 alternatively spliced mouse fast skeletal muscle troponin T isoforms","volume":"193","author":"Wang","year":"1997","journal-title":"Gene"},{"key":"10.1016\/j.nmd.2025.105415_bib0032","doi-asserted-by":"crossref","first-page":"14519","DOI":"10.1021\/bi9812322","article-title":"Conformational modulation of troponin T by configuration of the NH2-terminal variable region and functional effects","volume":"37","author":"Wang","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.nmd.2025.105415_bib0033","doi-asserted-by":"crossref","first-page":"27858","DOI":"10.1074\/jbc.273.43.27858","article-title":"Developmentally regulated, alternative RNA splicing-generated pectoral muscle-specific troponin T isoforms and role of the NH2-terminal hypervariable region in the tolerance to acidosis","volume":"273","author":"Ogut","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2025.105415_bib0034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2016.01.006","article-title":"TNNT1, TNNT2, and TNNT3: isoform genes, regulation, and structure-function relationships","volume":"582","author":"Wei","year":"2016","journal-title":"Gene"},{"key":"10.1016\/j.nmd.2025.105415_bib0035","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.747214","article-title":"Troponin variants as markers of skeletal muscle health and diseases","volume":"12","author":"Rasmussen","year":"2021","journal-title":"Front Physiol"},{"key":"10.1016\/j.nmd.2025.105415_bib0036","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/acn3.51816","article-title":"Muscle magnetic resonance imaging involvement patterns in nemaline myopathies","volume":"10","author":"Perry","year":"2023","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.nmd.2025.105415_bib0037","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1002\/acn3.52041","article-title":"Genome and RNA sequencing boost neuromuscular diagnoses to 62 % from 34 % with exome sequencing alone","volume":"11","author":"Marchant","year":"2024","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Neuromuscular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896625001427?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896625001427?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:54:49Z","timestamp":1777600489000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960896625001427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":37,"alternative-id":["S0960896625001427"],"URL":"https:\/\/doi.org\/10.1016\/j.nmd.2025.105415","relation":{},"ISSN":["0960-8966"],"issn-type":[{"value":"0960-8966","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Multi-omics approach identifies a novel recessive pathogenic variant in the TNNT3 gene in two siblings with congenital myopathy","name":"articletitle","label":"Article Title"},{"value":"Neuromuscular Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nmd.2025.105415","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"105415"}}