{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:08:06Z","timestamp":1781064486142,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["2021\u201002109"],"award-info":[{"award-number":["2021\u201002109"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Polyglucosan storage disorders represent an emerging field within neurodegenerative and neuromuscular conditions, including Lafora disease (<jats:italic>EPM2A<\/jats:italic>, <jats:italic>EPM2B<\/jats:italic>), adult polyglucosan body disease (APBD, <jats:italic>GBE1<\/jats:italic>), polyglucosan body myopathies associated with RBCK1 deficiency (PGBM1, <jats:italic>RBCK1<\/jats:italic>) or glycogenin\u20101 deficiency (PGBM2, <jats:italic>GYG1<\/jats:italic>). While the storage material primarily comprises glycans, this study aimed to gain deeper insights into the protein components by proteomic profiling of the storage material in glycogenin\u20101 deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed molecular genetic analyses, quantitative mass spectrometry of laser micro\u2010dissected polyglucosan bodies and muscle homogenate, immunohistochemistry and western blot analyses in muscle tissue from a 45\u2010year\u2010old patient with proximal muscle weakness from late teenage years due to polyglucosan storage myopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The muscle tissue exhibited a complete absence of glycogenin\u20101 due to a novel homozygous deep intronic variant in <jats:italic>GYG1<\/jats:italic> (c.7+992T&gt;G), introducing a pseudo\u2010exon causing frameshift and a premature stop codon. Accumulated proteins in the polyglucosan bodies constituted components of glycogen metabolism, protein quality control pathways and desmin. Muscle fibres containing polyglucosan bodies frequently exhibited depletion of normal glycogen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The absence of glycogenin\u20101, a protein important for glycogen synthesis initiation, causes storage of polyglucosan that displays accumulation of several proteins, including those essential for glycogen synthesis, sequestosome 1\/p62 and desmin, mirroring findings in RBCK1 deficiency. These results suggest shared pathogenic pathways across different diseases exhibiting polyglucosan storage. Such insights have implications for therapy in these rare yet devastating and presently untreatable disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12995","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T05:29:14Z","timestamp":1719293354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Proteomic profiling of polyglucosan bodies associated with glycogenin\u20101 deficiency in skeletal muscle"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-8533","authenticated-orcid":false,"given":"Kittichate","family":"Visuttijai","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Institute of Biomedicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-4185","authenticated-orcid":false,"given":"Carola","family":"Hedberg\u2010Oldfors","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Institute of Biomedicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6023-8246","authenticated-orcid":false,"given":"Daniel J.","family":"Costello","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cork University Hospital and College of Medicine and Health University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Bermingham","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Cork University Hospital  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-7397","authenticated-orcid":false,"given":"Anders","family":"Oldfors","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Institute of Biomedicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900661"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24284"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2015.08.006"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010016\u20109978\u20101"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2021.01.010"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12761"},{"key":"e_1_2_12_8_1","volume-title":"Muscle Biopsy: A Practical Approach","author":"Dubowitz V","year":"2021"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.017"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.264531"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010018\u20100057\u20100"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1739"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010022\u201001218\u20107"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac017"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010023\u201001434\u20109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.06.008"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.793328"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114554"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz032"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15864"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.10.002"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12865"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010016\u20108268\u2010z"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.07.007"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T04:52:15Z","timestamp":1719463935000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/nan.12995"],"URL":"https:\/\/doi.org\/10.1111\/nan.12995","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2024-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12995"}}