{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:23:07Z","timestamp":1791404587583,"version":"4.3.3"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Memorabel Zorgonderzoek Nederland","award":["733050507"],"award-info":[{"award-number":["733050507"]}]},{"DOI":"10.13039\/100000002","name":"National Institutions of Health","doi-asserted-by":"crossref","award":["R01NS086810"],"award-info":[{"award-number":["R01NS086810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutions of Health","doi-asserted-by":"crossref","award":["R01NS099280"],"award-info":[{"award-number":["R01NS099280"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Veterans affairs","award":["BLRD BX004842"],"award-info":[{"award-number":["BLRD BX004842"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CGG repeat expansions within the premutation range (55\u2013200) of the FMR1 gene can lead to Fragile X-associated tremor\/ataxia syndrome and Fragile X-associated neuropsychiatric disorders. These CGG repeats are translated into a toxic polyglycine-containing protein, FMRpolyG. Pathology of Fragile X-associated tremor\/ataxia syndrome and Fragile X-associated neuropsychiatric disorders comprises FMRpolyG- and p62-positive intranuclear inclusions. Diagnosing a FMR1-premutation carrier remains challenging, as the clinical features overlap with other neurodegenerative diseases. Here, we describe two male cases with Fragile X-associated neuropsychiatric disorders-related symptoms and mild movement disturbances and novel pathological features that can attribute to the variable phenotype. Macroscopically, both donors did not show characteristic white matter lesions on MRI; however, vascular infarcts in cortical- and sub-cortical regions were identified. Immunohistochemistry analyses revealed a high number of FMRpolyG intranuclear inclusions throughout the brain, which were also positive for p62. Importantly, we identified a novel pathological vascular phenotype with inclusions present in pericytes and endothelial cells. Although these results need to be confirmed in more cases, we propose that these vascular lesions in the brain could contribute to the complex symptomology of FMR1-premutation carriers. Overall, our report suggests that Fragile X-associated tremor\/ataxia syndrome and Fragile X-associated neuropsychiatric disorders may present diverse clinical involvements resembling other types of dementia, and in the absence of genetic testing, FMRpolyG can be used post-mortem to identify premutation carriers.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab007","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T15:48:34Z","timestamp":1611762514000},"source":"Crossref","is-referenced-by-count":12,"title":["Neuropathology of <i>FMR1<\/i>-premutation carriers presenting with dementia and neuropsychiatric symptoms"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-587X","authenticated-orcid":false,"given":"Anke A","family":"Dijkstra","sequence":"first","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience, Amsterdam University Medical Centre, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8812-7879","authenticated-orcid":false,"given":"Saif N","family":"Haify","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0013-6672","authenticated-orcid":false,"given":"Niek A","family":"Verwey","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels D","family":"Prins","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam Neuroscience, The Netherlands"},{"name":"Brain Research Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmay C","family":"van der Toorn","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke J M","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience, Amsterdam University Medical Centre, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Bugiani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience, Amsterdam University Medical Centre, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred F A","family":"den Dunnen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Veterans Affairs, Ann Arbor Healthcare System, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Charlet-Berguerand","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, University of Strasbourg, 67400, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-4154","authenticated-orcid":false,"given":"Renate K","family":"Hukema","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands"},{"name":"Department of Health Care Studies, Rotterdam University of Applied Sciences, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J M","family":"Hoozemans","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience, Amsterdam University Medical Centre, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"2021030619120213300_fcab007-B1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/jnen\/63.4.329","article-title":"Substantia nigra Marinesco bodies are associated with decreased striatal expression of dopaminergic markers","volume":"63","author":"Beach","year":"2004","journal-title":"J Neuropathol Exp 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