{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:49:03Z","timestamp":1790704143553,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-24-00555"],"award-info":[{"award-number":["23-24-00555"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arthrogryposis, which represents a group of congenital disorders, includes various forms. One such form is amyoplasia, which most commonly presents in a sporadic form in addition to distal forms, among which hereditary cases may occur. This condition is characterized by limited joint mobility and muscle weakness, leading to limb deformities and various clinical manifestations. At present, the pathogenesis of this disease is not clearly understood, and its diagnosis is often complicated due to significant phenotypic diversity, which can result in delayed detection and, consequently, limited options for symptomatic treatment. In this study, a transcriptomic analysis of the affected muscles from patients diagnosed with amyoplasia was performed, and more than 2000 differentially expressed genes (DEGs) were identified. A functional analysis revealed disrupted biological processes, such as vacuole organization, cellular and aerobic respiration, regulation of mitochondrion organization, cellular adhesion, ATP synthesis, and others. The search for key nodes (hubs) in protein\u2013protein interaction networks allowed for the identification of genes involved in mitochondrial processes.<\/jats:p>","DOI":"10.3390\/ijms26010124","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T19:33:07Z","timestamp":1735241587000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional Changes Associated with Amyoplasia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-1698","authenticated-orcid":false,"given":"Artem E.","family":"Komissarov","sequence":"first","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga E.","family":"Agranovich","sequence":"additional","affiliation":[{"name":"H. Turner National Medical Research Center for Children\u2019s Orthopedics and Trauma Surgery, Saint Petersburg 196603, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ianina A.","family":"Kuchinskaia","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Tkacheva","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-3014","authenticated-orcid":false,"given":"Olga I.","family":"Bolshakova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia M.","family":"Latypova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-8906","authenticated-orcid":false,"given":"Sergey F.","family":"Batkin","sequence":"additional","affiliation":[{"name":"H. Turner National Medical Research Center for Children\u2019s Orthopedics and Trauma Surgery, Saint Petersburg 196603, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3943-7504","authenticated-orcid":false,"given":"Svetlana V.","family":"Sarantseva","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ajmg.c.31721","article-title":"International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita","volume":"181","author":"Cachecho","year":"2019","journal-title":"Am. J. Med. Genet. C"},{"key":"ref_2","first-page":"e53993","article-title":"Arthrogryposis multiplex congenita and the importance of orthoses: A case report","volume":"16","author":"Gouveia","year":"2024","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s11832-015-0689-1","article-title":"AMC: Amyoplasia and distal arthrogryposis","volume":"9","author":"Kimber","year":"2015","journal-title":"J. Child. Orthop."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2106\/JBJS.I.00281","article-title":"Arthrogryposis: A review and update","volume":"91","author":"Bamshad","year":"2009","journal-title":"J. Bone Jt. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/ajmg.a.36395","article-title":"Amyoplasia revisited","volume":"164","author":"Hall","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/ajmg.1320150407","article-title":"Part I. Amyoplasia: A common, sporadic condition with congenital contractures","volume":"15","author":"Hall","year":"1983","journal-title":"Am. J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e299","DOI":"10.3928\/19382359-20200624-01","article-title":"Arthrogryposis multiplex congenita","volume":"49","author":"Langston","year":"2020","journal-title":"Pediatr. Ann."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00404-020-05828-4","article-title":"Prognostic significance of prenatal ultrasound in fetal arthrogryposis multiplex congenita","volume":"303","author":"Busack","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_9","first-page":"264918","article-title":"Diagnosing arthrogryposis multiplex congenita: A review","volume":"2012","author":"Kalampokas","year":"2012","journal-title":"Int. Sch. Res. Not."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jped.2015.04.008","article-title":"Characterization of a group of unrelated patients with arthrogryposis multiplex congenita","volume":"92","author":"Kofman","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0387-7604(98)00037-0","article-title":"Arthrogryposis multiplex congenita","volume":"20","author":"Gordon","year":"1998","journal-title":"Brain Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5114\/aoms.2016.57578","article-title":"Arthrogryposis: An update on clinical aspects, etiology, and treatment strategies","volume":"12","author":"Kowalczyk","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000446617","article-title":"Arthrogryposis as a syndrome: Gene ontology analysis","volume":"7","author":"Hall","year":"2016","journal-title":"Mol. Syndromol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/ng1775","article-title":"Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome","volume":"38","author":"Toydemir","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1096\/fj.06-6899com","article-title":"Mutations in fast skeletal troponin I, troponin T, and \u03b2-tropomyosin that cause distal arthrogryposis all increase contractile function","volume":"21","author":"Robinson","year":"2007","journal-title":"FASEB J."},{"key":"ref_16","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\u2013Hall syndrome in a Chinese family with vertical talus","volume":"54","author":"Zhao","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pollazzon, M., Caraffi, S.G., Faccioli, S., Rosato, S., Fodstad, H., Campos-Xavier, B., Soncini, E., Comitini, G., Frattini, D., and Grimaldi, T. (2021). Clinical and genetic findings in a series of eight families with arthrogryposis. Genes, 13.","DOI":"10.3390\/genes13010029"},{"key":"ref_18","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":"ref_19","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1097\/BPO.0000000000000997","article-title":"Genetics and classifications","volume":"37","author":"Hall","year":"2017","journal-title":"J. Pediatr. Orthop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/bdra.20738","article-title":"Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding","volume":"88","author":"Lowry","year":"2010","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102781","DOI":"10.1016\/j.otsr.2020.102781","article-title":"Amyoplasia and distal arthrogryposis","volume":"107","author":"Griffet","year":"2021","journal-title":"Orthop. Traumatol. Surg. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.ajhg.2015.04.014","article-title":"Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita","volume":"96","author":"Ravenscroft","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/hmg\/ddac254","article-title":"Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development","volume":"32","author":"Hale","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/geno.1999.6061","article-title":"Sequencing, expression analysis, and mapping of three unique human tropomodulin genes and their mouse orthologs","volume":"63","author":"Cox","year":"2000","journal-title":"Genomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.gene.2013.08.088","article-title":"The switch role of the Tmod4 in the regulation of balanced development between myogenesis and adipogenesis","volume":"532","author":"Zhao","year":"2013","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1080\/14767058.2017.1381683","article-title":"Arthrogryposis multiplex congenita in utero: Radiologic and pathologic findings","volume":"32","author":"Skaria","year":"2019","journal-title":"J. Matern. -Fetal Neonatal Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1126\/science.aaa1193","article-title":"The structure of the human mitochondrial ribosome","volume":"348","author":"Amunts","year":"2015","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Reid, K., Daniels, E.G., Vasam, G., Kamble, R., Janssens, G.E., Hu, I.M., Green, A.E., Houtkooper, R.H., and Menzies, K.J. (2023). Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35196-3"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huang, G., Li, H., and Zhang, H. (2020). Abnormal expression of mitochondrial ribosomal proteins and their encoding genes with cell apoptosis and diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228879"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1006\/geno.2001.6622","article-title":"The human mitochondrial ribosomal protein genes: Mapping of 54 genes to the chromosomes and implications for human disorders","volume":"77","author":"Kenmochi","year":"2001","journal-title":"Genomics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.semcdb.2017.08.011","article-title":"Building a complex complex: Assembly of mitochondrial respiratory chain complex I","volume":"76","author":"Formosa","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1002\/ajmg.a.35533","article-title":"Atypical amyoplasia congenita in an infant with Leigh syndrome: A mitochondrial cause of severe contractures?","volume":"158","author":"Wilnai","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0887-8994(97)00082-9","article-title":"Ragged-red fibers and complex I deficiency in a neonate with arthrogryposis congenita","volume":"17","author":"Laubscher","year":"1997","journal-title":"Pediatr. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/ajmg.a.31041","article-title":"Mitochondrial mutation in a child with distal arthrogryposis","volume":"140","author":"McPherson","year":"2006","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/00003086-198504000-00004","article-title":"The etiology of arthrogryposis (multiple congenital contracture)","volume":"194","author":"Swinyard","year":"1985","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Agerholm, J.S., McEvoy, F.J., Menzi, F., Jagannathan, V., and Dr\u00f6gem\u00fcller, C. (2016). A CHRNB1 frameshift mutation is associated with familial arthrogryposis multiplex congenita in Red dairy cattle. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2832-x"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Di Stasio, L., Albera, A., Pauciullo, A., Cesarani, A., Macciotta, N.P., and Gaspa, G. (2020). Genetics of Arthrogryposis and Macroglossia in Piemontese Cattle Breed. Animals, 10.","DOI":"10.3390\/ani10101732"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Whittle, J., Johnson, A., Dobbs, M.B., and Gurnett, C.A. (2021). Models of Distal Arthrogryposis and Lethal Congenital Contracture Syndrome. Genes, 12.","DOI":"10.3390\/genes12060943"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e12356","DOI":"10.15252\/emmm.202012356","article-title":"MYH 3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin","volume":"12","author":"Whittle","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13395-020-00241-6","article-title":"Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism","volume":"10","author":"Guo","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ydbio.2019.02.017","article-title":"Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila","volume":"449","author":"Das","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ajmg.c.31733","article-title":"Gene ontology analysis of arthrogryposis (multiple congenital contractures)","volume":"181","author":"Kiefer","year":"2019","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing high-throughput sequencing data in Python with HTSeq 2.0","volume":"38","author":"Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Anders, S., and Huber, W. (2010). Differential Expression Analysis for Sequence Count Data. Genome Biol., 11.","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-2"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","article-title":"cytoHubba: Identifying hub objects and sub-networks from complex interactome","volume":"8","author":"Chin","year":"2014","journal-title":"BMC Syst. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:00:50Z","timestamp":1760115650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010124"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010124","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,26]]}}}