Evidence map›Paper›PMID 25179228›Full record

ArticleNeurobiology of aging2015

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.

Pietro Fratta, James M Polke, Jia Newcombe, Sarah Mizielinska, Tammaryn Lashley, Mark Poulter, Jon Beck, Elisavet Preza, Anny Devoy, Katie Sidle and 20 more

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

Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
6.6field-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

27 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Unravelling the clinical spectrum and the role of repeat length inJournal of neurology, neurosurgery, and psychiatry · 2021
    Review
  10. Neurology · 2020
    Article
  11. Review
  12. Article
  13. The impact of histone post-translational modifications in neurodegenerative diseases.Biochimica et biophysica acta. Molecular basis of disease · 2019
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Disease Mechanisms ofCold Spring Harbor perspectives in medicine · 2018
    Review
  19. Unaffected mosaicNeurology · 2018
    Article
  20. Review
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

30 authors at 5 institutions in 2 countries.

Pietro FrattaDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, University College London, Queen Square, London, UK. Electronic address: p.fratta@ucl.ac.uk.
James M PolkeNeurogenetics Unit, Queen Square, London, UK. Electronic address: James.Polke@uclh.nhs.uk.
Jia NewcombeNeuroResource, Institute of Neurology, University College London, Queen Square, London, UK.
Sarah MizielinskaDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK.
Tammaryn LashleyQueen Square Brain Bank for Neurological Disorders, University College London, Queen Square, London, UK.
Mark PoulterDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Prion Unit, University College London, Queen Square, London, UK.
Jon BeckDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Prion Unit, University College London, Queen Square, London, UK.
Elisavet PrezaDepartment of Molecular Neuroscience, University College London, Queen Square, London, UK.
Anny DevoyDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK.
Katie SidleDepartment of Molecular Neuroscience, University College London, Queen Square, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Robin HowardNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Andrea MalaspinaNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Centre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.
Richard W OrrellMRC Centre for Neuromuscular Diseases, University College London, Queen Square, London, UK; Department of Molecular Neuroscience, University College London, Queen Square, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Jan ClarkeNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Ching-Hua LuCentre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK; Sobell Department of Motor Neuroscience and Movement Disorders, University College London, Queen Square, London, UK.
Kin MokSobell Department of Motor Neuroscience and Movement Disorders, University College London, Queen Square, London, UK.
Toby CollinsDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK.
Maryam ShoaiiDepartment of Molecular Neuroscience, University College London, Queen Square, London, UK.
Tina NanjiNeurogenetics Unit, Queen Square, London, UK.
Selina WrayDepartment of Molecular Neuroscience, University College London, Queen Square, London, UK.
Gary AdamsonDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Prion Unit, University College London, Queen Square, London, UK.
Alan PittmanDepartment of Molecular Neuroscience, University College London, Queen Square, London, UK.
Alan E RentonNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institutes of Health, National Institute on Aging, Bethesda, MD, USA.
Bryan J TraynorNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institutes of Health, National Institute on Aging, Bethesda, MD, USA.
Mary G SweeneyNeurogenetics Unit, Queen Square, London, UK.
Tamas ReveszQueen Square Brain Bank for Neurological Disorders, University College London, Queen Square, London, UK.
Henry HouldenNeurogenetics Unit, Queen Square, London, UK; Department of Molecular Neuroscience, University College London, Queen Square, London, UK.
Simon MeadDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK.
Adrian M IsaacsDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK.
Elizabeth M C FisherDepartment of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, University College London, Queen Square, London, UK. Electronic address: e.fisher@prion.ucl.ac.uk.
National Hospital for Neurology and Neurosurgery · GBMRC Prion Unit · GBQueen Mary University of London · GBNational Institutes of Health · USUniversity College London · GB

Funding

Genetic etiology of Fronto-Temporal Dementia, a dementia related to Alzheimers diseaseZIAAG000934 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$5.2M
Department of HealthMedical Research Council G0802760Medical Research Council G1000287Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MR/J004758/1Medical Research Council MR/K018523/1Medical Research Council MR/L021056/1Medical Research Council MR/M008606/1Motor Neurone Disease Association FRATTA/JAN15/946-795Motor Neurone Disease Association ISAACS/APR13/818-791
6 · The paper itself

Abstract

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD.

Indexed as

Cohort StudiesAmyotrophic Lateral SclerosisC9orf72 ProteinDNA Repeat ExpansionFrontotemporal DementiaHumansProteinsUnited KingdomC9orf72 ProteinC9orf72 protein, humanProteinsAmyotrophic lateral sclerosisFrontotemporal dementiaSomatic instability

Identifiers

PMID25179228
PMCPMC4270445
OpenAlexW2119943579

What OpenQuestion holds

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LicenceCC BY
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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.