{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:50:43Z","timestamp":1784029843418,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2017 SGR 324"],"award-info":[{"award-number":["2017 SGR 324"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["648201"],"award-info":[{"award-number":["648201"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Asuntos Econ\u00f3micos y Transformaci\u00f3n Digital, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PID2019\u2010110198RB\u2010I00"],"award-info":[{"award-number":["PID2019\u2010110198RB\u2010I00"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020\u2010114655RB\u2010I00"],"award-info":[{"award-number":["PID2020\u2010114655RB\u2010I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in <jats:italic>ANXA11<\/jats:italic> cause amyotrophic lateral sclerosis (ALS) and have recently been identified as a cause of multisystem proteinopathy and adult\u2010onset muscular dystrophy. These conditions are adult\u2010onset diseases and result from the substitution of Aspartate 40 (Asp40) for an apolar residue in the intrinsically disordered domain (IDD) of ANXA11. Some ALS\u2010related variants are known to affect ANXA11 IDD; however, the mechanism by which the myopathy occurs is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic analysis was performed using WES\u2010trio. For the study of variant pathogenicity, we used recombinant proteins, muscle biopsy, and fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we describe an individual with severe and rapidly progressive childhood\u2010onset oculopharyngeal muscular dystrophy who carries a new <jats:italic>ANXA11<\/jats:italic> variant at position Asp40 (p.Asp40Ile; c.118_119delGAinsAT). p.Asp40Ile is predicted to enhance the aggregation propensity of ANXA11 to a greater extent than other changes affecting this residue. In vitro studies using recombinant ANXA11<jats:sup>p.Asp40Ile<\/jats:sup> showed abnormal phase separation and confirmed this variant is more aggregation\u2010prone than the ALS\u2010associated variant ANXA11<jats:sup>p.Asp40Gly<\/jats:sup>. The study of the patient's fibroblasts revealed defects in stress granules dynamics and clearance, and muscle histopathology showed a myopathic pattern with ANXA11 protein aggregates. Super\u2010resolution imaging showed aggregates expressed as pearl strips or large complex structures in the sarcoplasm, and as layered subsarcolemmal chains probably reflecting ANXA11 multifunctionality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We demonstrate common pathophysiology for disorders associated with <jats:italic>ANXA11<\/jats:italic> Asp40 allelic variants. Clinical phenotypes may result from different deleterious impacts of variants upon ANXA11 stability against aggregation, and differential muscle or motor neuron dysfunction expressed as a temporal and tissue\u2010specific continuum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51731","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T12:48:48Z","timestamp":1674046128000},"page":"408-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Common pathophysiology for <scp>ANXA11<\/scp> disorders caused by aspartate 40 variants"],"prefix":"10.1002","volume":"10","author":[{"given":"Daniel","family":"Natera\u2010de Benito","sequence":"first","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Olival","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Molecular Medicine \u2013 IPER Institut de Recerca Sant Joan de D\u00e9u  08950 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Garcia\u2010Cabau","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology  Barcelona 08029 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Jou","sequence":"additional","affiliation":[{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Department of Pathology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f2nica","family":"Roldan","sequence":"additional","affiliation":[{"name":"Confocal Microscopy and Cellular Imaging Unit Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Department of Genetics and Developmental Medicine \u2013 IPER Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Codina","sequence":"additional","affiliation":[{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Exp\u00f3sito\u2010Escudero","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Batlle","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Molecular Medicine \u2013 IPER Institut de Recerca Sant Joan de D\u00e9u  08950 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carrera\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ortez","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER) ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Salvatella","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology  Barcelona 08029 Spain"},{"name":"ICREA  Barcelona 08010 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Palau","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Molecular Medicine \u2013 IPER Institut de Recerca Sant Joan de D\u00e9u  08950 Barcelona Spain"},{"name":"Department of Genetics and Developmental Medicine \u2013 IPER Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER) ISCIII  Barcelona Spain"},{"name":"Division of Pediatrics, Faculty of Medicine and Health Sciences University of Barcelona  Barcelona 08007 Spain"},{"name":"ERN ITHACA  Barcelona 08950 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Applied Research in Neuromuscular Diseases Institut de Recerca Sant Joan de D\u00e9u  Barcelona 08950 Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER) ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-6988","authenticated-orcid":false,"given":"Janet","family":"Hoenicka","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Molecular Medicine \u2013 IPER Institut de Recerca Sant Joan de D\u00e9u  08950 Barcelona Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER) ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050065"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-4-219"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1661"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.01.031"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.050"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax3993"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092247"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad9157"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000237"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26136"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51665"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1332"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11922"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001864"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.006"},{"key":"e_1_2_9_17_1","article-title":"hnRNPA2B1 cause early\u2010onset oculopharyngeal muscular dystrophy","author":"Kim HJ","year":"2021","journal-title":"medRxiv"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa794"},{"key":"e_1_2_9_30_1","volume-title":"Muscle Biopsy: A Practical Approach","author":"Dubowitz V","year":"2013"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO;2-3"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0694-399"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-65"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.06.038"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-6-62"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30015-1"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200011)48:5<812::AID-ANA20>3.0.CO;2-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah5436"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15280"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00678-1"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.055"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15276"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11070671"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51731","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51731","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51731","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T03:14:24Z","timestamp":1692587664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/acn3.51731"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51731","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]},"assertion":[{"value":"2022-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}