{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:51:24Z","timestamp":1781646684551,"version":"3.54.5"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006254","name":"Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006254","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Desminopathies are clinical heterogenous and range from isolated skeletal myopathies to different cardiomyopathies or combinations of both. At the molecular level, an aberrant cytoplasmic desmin aggregation is a typical hallmark of pathogenic\n                      <jats:italic>DES<\/jats:italic>\n                      variants. Currently, it is difficult to predict an aberrant desmin aggregation of novel\n                      <jats:italic>DES<\/jats:italic>\n                      variants without functional analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Therefore, we investigate in this study the impact of an uncharacterized myofibrillar myopathy-associated desmin variant (p.T341P) on filament assembly in transfected cells and performed atomic force microscopy to characterize in vitro the filament assembly of recombinant desmin-p.T341P.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Based on these cell transfection experiments using different cell lines and cardiomyocytes differentiated from induced pluripotent stem cells (iPSC) we present evidence that the filament assembly of desmin-p.T341P is disrupted. In addition, atomic force microscopy (AFM) analysis revealed aberrant molecular structures of recombinant desmin in comparison to wild-type desmin. These experiments showed an intrinsic filament assembly defect of desmin-p.T341P. Therefore, we suggest to classify this\n                      <jats:italic>DES<\/jats:italic>\n                      variant as a likely pathogenic variant associated with myofibrillar myopathy and heart failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion, functional analysis of the desmin filament assembly can contribute to the pathogenicity classification of further\n                      <jats:italic>DES<\/jats:italic>\n                      variants and may be helpful in genetic counselling of affected patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-11696-z","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:02:47Z","timestamp":1774436567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The myofibrillar myopathy\u2013linked variant DES-p.T341P impairs desmin filament assembly"],"prefix":"10.1007","volume":"53","author":[{"given":"Alexander","family":"L\u00fctkemeyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Vo\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Klag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joline","family":"Gro\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Reckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"G\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Anselmetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Gummert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Walhorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Milting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Brodehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"issue":"3","key":"11696_CR1","doi-asserted-by":"publisher","first-page":"e004896","DOI":"10.1161\/CIRCGEN.124.004896","volume":"18","author":"MA Ebrahim","year":"2025","unstructured":"Ebrahim MA et al (2025) Phenotypic diversity caused by the DES missense mutation p.R127P (c.380G\u2009>\u2009C) Contributing to significant cardiac mortality and morbidity associated with a desmin filament assembly defect. Circ Genom Precis Med 18(3):e004896","journal-title":"Circ Genom Precis Med"},{"issue":"2","key":"11696_CR2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/mgg3.358","volume":"6","author":"I Schirmer","year":"2018","unstructured":"Schirmer I et al (2018) A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Mol Genet Genomic Med 6(2):288\u2013293","journal-title":"Mol Genet Genomic Med"},{"key":"11696_CR3","doi-asserted-by":"publisher","unstructured":"BrodehlA et al (2021) The desmin mutation DES-c.735G\u2009>\u2009C causes severe restrictive cardiomyopathy by inducing in-frame skipping of Exon-3. Biomedicines, 9(10):1400 https:\/\/doi.org\/10.3390\/biomedicines9101400","DOI":"10.3390\/biomedicines9101400"},{"issue":"5","key":"11696_CR4","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1002\/1531-8249(199911)46:5<681::AID-ANA1>3.0.CO;2-B","volume":"46","author":"AG Engel","year":"1999","unstructured":"Engel AG (1999) Myofibrillar myopathy. Ann Neurol 46(5):681\u2013683","journal-title":"Ann Neurol"},{"issue":"4","key":"11696_CR5","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s13353-018-0463-4","volume":"59","author":"JP Fichna","year":"2018","unstructured":"Fichna JP, Maruszak A, Zekanowski C (2018) Myofibrillar myopathy in the genomic context. J Appl Genet 59(4):431\u2013439","journal-title":"J Appl Genet"},{"key":"11696_CR6","doi-asserted-by":"publisher","unstructured":"Castaneda SL et al (2025) Novel in-frame variant in DES (p.Glu353dup) causes myofibrillar myopathy: clinical, in silico and functional studies. J Med Genet31:jmg-2025-110852. https:\/\/doi.org\/10.1136\/jmg-2025-110852","DOI":"10.1136\/jmg-2025-110852"},{"issue":"11","key":"11696_CR7","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1056\/NEJM200003163421104","volume":"342","author":"MC Dalakas","year":"2000","unstructured":"Dalakas MC et al (2000) Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med 342(11):770\u2013780","journal-title":"N Engl J Med"},{"issue":"4","key":"11696_CR8","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1007\/s12551-018-0429-0","volume":"10","author":"A Brodehl","year":"2018","unstructured":"Brodehl A, Gaertner-Rommel A, Milting H (2018) Molecular insights into cardiomyopathies associated with desmin (DES) mutations. Biophys Rev 10(4):983\u20131006","journal-title":"Biophys Rev"},{"key":"11696_CR9","doi-asserted-by":"publisher","unstructured":"Dayal AA et al (2020) Desmin interacts directly with mitochondria. Int J Mol Sci, 21(21):8122. https:\/\/doi.org\/10.3390\/ijms21218122","DOI":"10.3390\/ijms21218122"},{"issue":"7","key":"11696_CR10","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1172\/JCI38027","volume":"119","author":"LG Goldfarb","year":"2009","unstructured":"Goldfarb LG, Dalakas MC (2009) Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. J Clin Invest 119(7):1806\u20131813","journal-title":"J Clin Invest"},{"issue":"1","key":"11696_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yexcr.2004.08.004","volume":"301","author":"D Paulin","year":"2004","unstructured":"Paulin D, Li Z (2004) Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle. Exp Cell Res 301(1):1\u20137","journal-title":"Exp Cell Res"},{"key":"11696_CR12","unstructured":"Pauls VY (2019) A review of clinical data of family form of myofibrillar desmin myopathy. Syst Reviews Pharm, 10(2)."},{"issue":"2","key":"11696_CR13","first-page":"265","volume":"15","author":"VY Pauls","year":"2023","unstructured":"Pauls VY (2023) Change characteristics in saliva and feces microbiota of a desminopathy T341P Patient. Siberian J Life Sci Agric 15(2):265\u2013283","journal-title":"Siberian J Life Sci Agric"},{"issue":"1","key":"11696_CR14","doi-asserted-by":"publisher","first-page":"101","DOI":"10.46235\/1028-7221-16974-FOA","volume":"29","author":"VY Pauls","year":"2026","unstructured":"Pauls VY (2026) Features of allergic status in a patient with T341P desminopathy. Russ J Immunol 29(1):101\u2013112","journal-title":"Russ J Immunol"},{"issue":"19","key":"11696_CR15","doi-asserted-by":"publisher","first-page":"16047","DOI":"10.1074\/jbc.M111.313841","volume":"287","author":"A Brodehl","year":"2012","unstructured":"Brodehl A et al (2012) Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem 287(19):16047\u201316057","journal-title":"J Biol Chem"},{"issue":"1","key":"11696_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nprot.2012.150","volume":"8","author":"X Lian","year":"2013","unstructured":"Lian X et al (2013) Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt\/beta-catenin signaling under fully defined conditions. Nat Protoc 8(1):162\u2013175","journal-title":"Nat Protoc"},{"key":"11696_CR17","doi-asserted-by":"crossref","unstructured":"Voss S et al (2025) Atlas of cardiomyopathy associated DES (Desmin) mutations: functional insights into the critical 1B domain. Circ Genom Precis Med e005358","DOI":"10.1101\/2025.09.19.25335981"},{"issue":"6","key":"11696_CR18","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/s41594-024-01261-2","volume":"31","author":"M Eibauer","year":"2024","unstructured":"Eibauer M et al (2024) Vimentin filaments integrate low-complexity domains in a complex helical structure. Nat Struct Mol Biol 31(6):939\u2013949","journal-title":"Nat Struct Mol Biol"},{"key":"11696_CR19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-3-032-05273-5_6","volume":"113","author":"M Eibauer","year":"2026","unstructured":"Eibauer M, Medalia O (2026) Insights into the structure of intermediate filaments. Subcell Biochem 113:143\u2013161","journal-title":"Subcell Biochem"},{"issue":"W1","key":"11696_CR20","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse A et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46(W1):W296\u2013W303","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"11696_CR21","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/0014-4827(86)90081-9","volume":"163","author":"KK Hedberg","year":"1986","unstructured":"Hedberg KK, Chen LB (1986) Absence of intermediate filaments in a human adrenal cortex carcinoma-derived cell line. Exp Cell Res 163(2):509\u2013517","journal-title":"Exp Cell Res"},{"issue":"42","key":"11696_CR22","doi-asserted-by":"publisher","first-page":"15099","DOI":"10.1073\/pnas.0504568102","volume":"102","author":"H Bar","year":"2005","unstructured":"Bar H et al (2005) Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages. Proc Natl Acad Sci U S A 102(42):15099\u201315104","journal-title":"Proc Natl Acad Sci U S A"},{"key":"11696_CR23","doi-asserted-by":"publisher","unstructured":"Brodehl A et al (2022) The N-terminal part of the 1A domain of desmin is a hot spot region for putative pathogenic DES mutations affecting filament assembly. Cells, 11(23):3906. https:\/\/doi.org\/10.3390\/cells11233906","DOI":"10.3390\/cells11233906"},{"issue":"1","key":"11696_CR24","doi-asserted-by":"publisher","first-page":"101238","DOI":"10.1016\/j.gendis.2024.101238","volume":"12","author":"S Voss","year":"2025","unstructured":"Voss S et al (2025) Functional impact of the head domain variants of DES (Desmin) on filament assembly. Genes Dis 12(1):101238","journal-title":"Genes Dis"},{"key":"11696_CR25","doi-asserted-by":"crossref","unstructured":"Reckmann J et al (2025) Cardiomyopathy-associated mutations in a hotspot region at the C-terminal part of desmin coil-2 domain impair the intermediate filament assembly. medRxiv 2025-12.","DOI":"10.64898\/2025.12.15.25342325"},{"issue":"5","key":"11696_CR26","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405\u2013424","journal-title":"Genet Med"},{"issue":"1","key":"11696_CR27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13073-019-0690-2","volume":"12","author":"SE Brnich","year":"2019","unstructured":"Brnich SE et al (2019) Recommendations for application of the functional evidence PS3\/BS3 criterion using the ACMG\/AMP sequence variant interpretation framework. Genome Med 12(1):3","journal-title":"Genome Med"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-11696-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-026-11696-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-11696-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:51:29Z","timestamp":1781643089000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-026-11696-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["11696"],"URL":"https:\/\/doi.org\/10.1007\/s11033-026-11696-z","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"19 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A.B. is a shareholder of Merck, Prime Medicine and Tenaya Therapeutics. The remaining authors have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not relevant.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}],"article-number":"539"}}