Evidence map›Paper›PMID 31870437›Full record

ArticleActa neuropathologica communications2019

Investigation of somatic CNVs in brains of synucleinopathy cases using targeted SNCA analysis and single cell sequencing.

Diego Perez-Rodriguez, Maria Kalyva, Melissa Leija-Salazar, Tammaryn Lashley, Maxime Tarabichi, Viorica Chelban, Steve Gentleman, Lucia Schottlaender, Hannah Franklin, George Vasmatzis and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 50 citations in OpenAlex.

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  12. The genetic basis of multiple system atrophy.Journal of translational medicine · 2023
    Review
  13. Article
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  15. Multiple system atrophy.Nature reviews. Disease primers · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Diego Perez-RodriguezDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Maria KalyvaDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Melissa Leija-SalazarDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Tammaryn LashleyQueen Square Brain Bank for Neurological disorders, UCL Queen Square Institute of Neurology, 1 Wakefield street, London, WC1N 1PJ, UK.
Maxime TarabichiThe Francis Crick Institute, Midland Road 1, London, NW1 1AT, UK.
Viorica ChelbanDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Steve GentlemanDepartment of Medicine, Imperial College London, London, UK.
Lucia SchottlaenderDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Hannah FranklinDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
George VasmatzisCenter for Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Anthony H V SchapiraDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Thomas T WarnerDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Janice L HoltonDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Zane JaunmuktaneDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Christos ProukakisDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK. c.proukakis@ucl.ac.uk.ORCID 0000-0001-6423-6539
National Hospital for Neurology and Neurosurgery · GBImperial College London · GBMayo Clinic · USThe Francis Crick Institute · GBUK Dementia Research Institute · GB

Funding

Cancer Research UK FC001202Department of Health [UK]Medical Research Council FC001202Medical Research Council G0802760Medical Research Council G1001253Medical Research Council MR/J004758/1Medical Research Council MR/S01165X/1Michael J. Fox Foundation for Parkinson's Research 8811.2Wellcome Trust FC001202Wellcome Trust WT093205MAWellcome Trust WT104033/Z/14/Z
6 · The paper itself

Abstract

Synucleinopathies are mostly sporadic neurodegenerative disorders of partly unexplained aetiology, and include Parkinson's disease (PD) and multiple system atrophy (MSA). We have further investigated our recent finding of somatic SNCA (α-synuclein) copy number variants (CNVs, specifically gains) in synucleinopathies, using Fluorescent in-situ Hybridisation for SNCA, and single-cell whole genome sequencing for the first time in a synucleinopathy. In the cingulate cortex, mosaicism levels for SNCA gains were higher in MSA and PD than controls in neurons (> 2% in both diseases), and for MSA also in non-neurons. In MSA substantia nigra (SN), we noted SNCA gains in > 3% of dopaminergic (DA) neurons (identified by neuromelanin) and neuromelanin-negative cells, including olig2-positive oligodendroglia. Cells with CNVs were more likely to have α-synuclein inclusions, in a pattern corresponding to cell categories mostly relevant to the disease: DA neurons in Lewy-body cases, and other cells in the striatonigral degeneration-dominant MSA variant (MSA-SND). Higher mosaicism levels in SN neuromelanin-negative cells may correlate with younger onset in typical MSA-SND, and in cingulate neurons with younger death in PD. Larger sample sizes will, however, be required to confirm these putative findings. We obtained genome-wide somatic CNV profiles from 169 cells from the substantia nigra of two MSA cases, and pons and putamen of one. These showed somatic CNVs in ~ 30% of cells, with clonality and origins in segmental duplications for some. CNVs had distinct profiles based on cell type, with neurons having a mix of gains and losses, and other cells having almost exclusively gains, although control data sets will be required to determine possible disease relevance. We propose that somatic SNCA CNVs may contribute to the aetiology and pathogenesis of synucleinopathies, and that genome-wide somatic CNVs in MSA brain merit further study.

Indexed as

DNA Copy Number Variationsalpha-SynucleinBrainGyrus CinguliHumansMaleMultiple System AtrophyNeuronsParkinson DiseaseSingle-Cell Analysisalpha-SynucleinSNCA protein, humanAlpha-synucleinMosaicismMultiple system atrophyParkinson’s diseaseSingle cell sequencingSNCASomatic mutation

Identifiers

PMID31870437
PMCPMC6929293
OpenAlexW2996708502

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.