TY  - INPR
UR  - https://doi.org/10.1002/mds.29291
KW  - alpha-synuclein
KW  -  mosaicism
KW  -  multiple system atrophy
KW  -  snca
KW  -  somatic mutation
TI  - Somatic SNCA Copy Number Variants in Multiple System Atrophy Are Related to Pathology and Inclusions
ID  - discovery10161354
N1  - © 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.
SN  - 0885-3185
JF  - Movement Disorders
AV  - public
N2  - BACKGROUND: Somatic ?-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 ?-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.
PB  - Wiley
Y1  - 2022/11/30/
A1  - Garcia-Segura, Monica Emili
A1  - Perez-Rodriguez, Diego
A1  - Chambers, Darren
A1  - Jaunmuktane, Zane
A1  - Proukakis, Christos
ER  -