{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:02:28Z","timestamp":1787828548790,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016944","name":"Regenerative Medicine Minnesota","doi-asserted-by":"publisher","award":["P008848103"],"award-info":[{"award-number":["P008848103"]}],"id":[{"id":"10.13039\/100016944","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":[[2023,4]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n \n Mutations in\n VCP, HNRNPA2B1, HNRNPA1<\/jats:italic>\n , and\n SQSTM1<\/jats:italic>\n , encoding RNA\u2010binding proteins or proteins in quality\u2010control pathways, cause multisystem proteinopathies (MSP). They share pathological findings of protein aggregation and clinical combinations of inclusion body myopathy (IBM), neurodegeneration [motor neuron disorder (MND)\/frontotemporal dementia (FTD)], and Paget disease of bone (PDB). Subsequently, additional genes were linked to similar but not full clinical\u2010pathological spectrum (MSP\u2010like disorders). We aimed to define the phenotypic\u2010genotypic spectrum of MSP and MSP\u2010like disorders at our institution, including long\u2010term follow\u2010up features.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We searched the Mayo Clinic database (January 2010\u2013June 2022) to identify patients with mutations in MSP and MSP\u2010like disorders causative genes. Medical records were reviewed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty\u2010one individuals (27 families) had pathogenic mutations in:\n VCP<\/jats:italic>\n (\n n<\/jats:italic>\n \u00a0=\u200917),\n SQSTM1\u2009+\u2009TIA1<\/jats:italic>\n (\n n<\/jats:italic>\n \u00a0=\u20095),\n TIA1<\/jats:italic>\n (\n n<\/jats:italic>\n \u00a0=\u20095),\n MATR3, HNRNPA1, HSPB8<\/jats:italic>\n , and\n TFG<\/jats:italic>\n (\n n<\/jats:italic>\n \u00a0=\u20091, each). Myopathy occurred in all but 2\n VCP<\/jats:italic>\n \u2010MSP patients with disease onset at age 52 (median). Weakness pattern was limb\u2010girdle in 12\/15\n VCP<\/jats:italic>\n \u2010MSP and\n HSPB8<\/jats:italic>\n patient, and distal\u2010predominant in other MSP and MSP\u2010like disorders. Twenty\/24 muscle biopsies showed rimmed vacuolar myopathy. MND and FTD occurred in 5 (4\n VCP<\/jats:italic>\n , 1\n TFG<\/jats:italic>\n ) and 4 (3\n VCP<\/jats:italic>\n ,\n 1 SQSTM1\u2009+\u2009TIA1<\/jats:italic>\n ) patients, respectively. PDB manifested in 4\n VCP<\/jats:italic>\n \u2010MSP. Diastolic dysfunction occurred in 2\n VCP<\/jats:italic>\n \u2010MSP. After 11.5\u2009years (median) from symptom onset, 15 patients ambulated without gait\u2010aids; loss of ambulation (\n n<\/jats:italic>\n \u00a0=\u20095) and death (\n n<\/jats:italic>\n \u00a0=\u20093) were recorded only in\n VCP<\/jats:italic>\n \u2010MSP.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n VCP<\/jats:italic>\n \u2010MSP was the most common disorder; rimmed vacuolar myopathy was the most frequent manifestation; distal\u2010predominant weakness occurred frequently in non\u2010\n VCP<\/jats:italic>\n \u2010MSP; and cardiac involvement was observed only in\n VCP<\/jats:italic>\n \u2010MSP.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.51751","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T02:21:36Z","timestamp":1677723696000},"page":"632-643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Multisystem proteinopathies (MSPs) and MSP\u2010like disorders: Clinical\u2010pathological\u2010molecular spectrum"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-2372","authenticated-orcid":false,"given":"Pitcha","family":"Chompoopong","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Oskarsson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas N.","family":"Madigan","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igal","family":"Mirman","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota 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