eprintid: 10161354
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/16/13/54
datestamp: 2022-12-06 11:30:04
lastmod: 2024-11-11 16:38:05
status_changed: 2022-12-06 11:30:04
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Garcia-Segura, Monica Emili
creators_name: Perez-Rodriguez, Diego
creators_name: Chambers, Darren
creators_name: Jaunmuktane, Zane
creators_name: Proukakis, Christos
title: Somatic SNCA Copy Number Variants in Multiple System Atrophy Are Related to Pathology and Inclusions
ispublished: inpress
subjects: UCH
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F84
keywords: alpha-synuclein, mosaicism, multiple system atrophy, snca, somatic mutation
note: © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
abstract: BACKGROUND: Somatic α-synuclein (SNCA) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains. OBJECTIVE: The aim was to compare somatic SNCA CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions. METHODS: We combined fluorescent in situ hybridization with immunofluorescence for α-synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP). RESULTS: 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. CONCLUSIONS: The correlation between SNCA CNVs and pathology (at a regional level) and inclusions (at a single-cell level) suggests a role for somatic SNCA CNVs in MSA pathogenesis. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
date: 2022-11-30
date_type: published
publisher: Wiley
official_url: https://doi.org/10.1002/mds.29291
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1993399
doi: 10.1002/mds.29291
medium: Print-Electronic
lyricists_name: Proukakis, Christos
lyricists_name: Jaunmuktane, Zane
lyricists_id: CPROU78
lyricists_id: ZJAUN70
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
funding_acknowledgements: [Multiple System Atrophy Trust]
full_text_status: public
publication: Movement Disorders
event_location: United States
issn: 0885-3185
citation:        Garcia-Segura, Monica Emili;    Perez-Rodriguez, Diego;    Chambers, Darren;    Jaunmuktane, Zane;    Proukakis, Christos;      (2022)    Somatic SNCA Copy Number Variants in Multiple System Atrophy Are Related to Pathology and Inclusions.                   Movement Disorders        10.1002/mds.29291 <https://doi.org/10.1002/mds.29291>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10161354/1/Somatic%20SNCA%20Copy%20Number%20Variants%20in%20Multiple%20System%20Atrophy.pdf