Media type: E-Article Title: Somatic SNCA Copy Number Variants in Multiple System Atrophy are Related to Pathology and Inclusions Contributor: Garcia‐Segura, Monica Emili; Perez‐Rodriguez, Diego; Chambers, Darren; Jaunmuktane, Zane; Proukakis, Christos imprint: Wiley, 2023 Published in: Movement Disorders Language: English DOI: 10.1002/mds.29291 ISSN: 0885-3185; 1531-8257 Keywords: Neurology (clinical) ; Neurology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Somatic α‐synuclein (<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 α‐synuclein 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‐cell level) suggests a role for somatic <jats:italic>SNCA</jats:italic> CNVs in MSA pathogenesis. © 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>