{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:25:27Z","timestamp":1789428327578,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Somatic \u03b1\u2010synuclein (<jats:italic>SNCA<\/jats:italic>) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim was to compare somatic <jats:italic>SNCA<\/jats:italic> CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We combined fluorescent in situ hybridization with immunofluorescence for \u03b1\u2010synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We analyzed one to three brain regions from 24 MSA cases (13 SND, 11 OPCA). In a region preferentially affected in one subtype (putamen in SND, cerebellum in OPCA), mosaicism was higher in that subtype, and cells with CNVs were 4.2 times more likely to have inclusions. In the substantia nigra, nonpigmented cells with CNVs and TPPP were about six times more likely to have inclusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The correlation between <jats:italic>SNCA<\/jats:italic> CNVs and pathology (at a regional level) and inclusions (at a single\u2010cell level) suggests a role for somatic <jats:italic>SNCA<\/jats:italic> CNVs in MSA pathogenesis. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29291","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:00:26Z","timestamp":1669791626000},"page":"338-342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Somatic <scp><i>SNCA<\/i><\/scp> Copy Number Variants in Multiple System Atrophy are Related to Pathology and Inclusions"],"prefix":"10.1002","volume":"38","author":[{"given":"Monica Emili","family":"Garcia\u2010Segura","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4903-3914","authenticated-orcid":false,"given":"Diego","family":"Perez\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0200-9274","authenticated-orcid":false,"given":"Darren","family":"Chambers","sequence":"additional","affiliation":[{"name":"The Dubowitz Neuromuscular Centre, Division of Neuropathology, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-8881","authenticated-orcid":false,"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London UK"},{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology University College London  London UK"},{"name":"Division of Neuropathology, National Hospital for Neurology and Neurosurgery University College London NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6423-6539","authenticated-orcid":false,"given":"Christos","family":"Proukakis","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London 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