ArticleNeuron2021
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
Open access · bronzeAbstract read
In one paragraph
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 3% of its field
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.
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.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.Disease models & mechanisms · 2022Pooled it
- Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.International journal of molecular sciences · 2026Article
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Prevalence and impact of comorbidities in amyotrophic lateral sclerosis.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Short tandem repeat expansions in patients with neurodegenerative dementia.EBioMedicine · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis.Nature medicine · 2025Article
- Concurrent Amyotrophic Lateral Sclerosis and Huntington's Disease.Internal medicine (Tokyo, Japan) · 2025Article
- The role of disease-associated short tandem repeats in amyotrophic lateral sclerosis.Brain communications · 2025Article
- Tandem repeat expansions and copy number variations as risk factors and diagnostic tools for amyotrophic lateral sclerosis.Frontiers in neurology · 2025Review
- Significant underascertainment in Huntington's disease.Brain communications · 2025Article
- Genetic testing for monogenic forms of motor neuron disease/amyotrophic lateral sclerosis in unaffected family members.European journal of human genetics : EJHG · 2025Review
- IntermediateJournal of neurology, neurosurgery, and psychiatry · 2024Article
- Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.Journal of neurology · 2024Article
- Pathogenic TDP-43 accelerates the generation of toxic exon1 HTT in Huntington's disease knock-in mice.Aging cell · 2024Article
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.Cell genomics · 2024Article
- Small striatal huntingtin inclusions in patients with motor neuron disease with reduced penetrance and intermediate HTT gene expansions.Human molecular genetics · 2024Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
57 authors at 20 institutions in 6 countries.
Ramita DewanNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Ruth ChiaNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Jinhui DingComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Richard A HickmanDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Thor D SteinDepartment of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA; Research and Development Service, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA; Department of Veterans Affairs Medical Center, Bedford, MA 01730, USA.
Yevgeniya AbramzonNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK.
Sarah AhmedNeurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Marya S SabirNeurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Makayla K PortleyNeurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Arianna TucciClinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Kristina IbáñezClinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
F N U ShankaracharyaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pamela KeagleDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Giacomina RossiDivision of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Paola CaroppoDivision of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Fabrizio TagliaviniScientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Maria L WaldoDivision of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Lund 221 84, Sweden.
Per M JohanssonDivision of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Lund 221 84, Sweden; Department of Internal Medicine, Sahlgrenska Academy, University of Gottenburg, Gottenburg 413 45, Sweden.
Christer F NilssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, 205 02 Malmö, Sweden.
American Genome Center (TAGC)
FALS Sequencing Consortium
Genomics England Research Consortium
International ALS/FTD Genomics Consortium (iAFGC)
International FTD Genetics Consortium (IFGC)
International LBD Genomics Consortium (iLBDGC)
NYGC ALS Consortium
PROSPECT ConsortiumCambridge University Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge Biomedical Campus, Cambridge CB2 02Z, UK.
James B RoweCambridge University Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge Biomedical Campus, Cambridge CB2 02Z, UK.
Luisa BenussiMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy.
Giuliano BinettiMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy; MAC Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy.
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy.
Edwin JabbariDepartment of Neurology, Royal Free Hospital, London NW3 2PF, UK; Department of Clinical and Movement Neuroscience, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Coralie ViolletDepartment of Anatomy, Physiology and Genetics, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Jonathan D GlassDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Andrew B SingletonMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Vincenzo SilaniDepartment of Neurology - Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan 20122, Italy.
Owen A RossDepartment of Neuroscience & Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USA.
Mina RytenReta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1E 6BT, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 3JH, UK.
Ali TorkamaniThe Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA 92037, USA.
Toshiko TanakaLongitudinal Studies Section, National Institute on Aging, Baltimore, MD 21224, USA.
Luigi FerrucciLongitudinal Studies Section, National Institute on Aging, Baltimore, MD 21224, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD 21224, USA.
Stuart Pickering-BrownDivision of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK.
Christopher B BradyDepartment of Neurology & Program in Behavioral Neuroscience, Boston University School of Medicine, Boston, MA 02118, USA; Research and Development Service, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA.
Neil KowalDepartment of Neurology, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA.
John A HardyReta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; UK Dementia Research Institute at UCL and Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; NINR University College London Hospitals Biomedical Research Centre, University College London, London W1T 7DN, UK; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
Vivianna Van DeerlinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jean Paul VonsattelDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Matthew B HarmsDepartment of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Huw R MorrisDepartment of Neurology, Royal Free Hospital, London NW3 2PF, UK; Department of Clinical and Movement Neuroscience, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Raffaele FerrariDepartment of Neurology, Royal Free Hospital, London NW3 2PF, UK.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Adriano ChiòRita Levi Montalcini Department of Neuroscience, University of Turin, Turin 10126, Italy; Institute of Cognitive Sciences and Technologies, C.N.R., Rome 00185, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin 10126, Italy.
J Raphael GibbsComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Clifton L DalgardDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Sonja W ScholzNeurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA.
Bryan J TraynorNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA. Electronic address: traynorb@mail.nih.gov.
National Institute on Aging · USCentro San Giovanni di Dio Fatebenefratelli · ITColumbia University Irving Medical Center · USThe Royal Free Hospital · GBBoston University · USUniversity of Massachusetts Chan Medical School · USNational Institute of Neurological Disorders and Stroke · USAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITEmory University · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITLund University · SECambridge University Hospitals NHS Foundation Trust · GBJohns Hopkins University · USUniversity of Pennsylvania · USQueen Mary University of London · GBUniformed Services University of the Health Sciences · USUniversity of Manchester · GBUniversity of Milan · ITGreat Ormond Street Hospital · GBHong Kong University of Science and Technology · HK
Funding
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI NIKOLAOS K ROBAKIS · 2020 to 2026
$31.0MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Andrew Franklin Teich · 2020 to 2026
$30.1MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3MNeuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BIGIO, EILEEN H. · 1996 to 2020
$28.9MBiomarkers of Parkinson Disease and Related DisordersZIANS003034 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI GOLDSTEIN, DAVID · 2009 to 2025
$22.8MEarly Markers of Alzheimer DiseaseZIAAG000185 · NIA · NATIONAL INSTITUTE ON AGING · PI WALKER, KEENAN · 2009 to 2025
$20.4MUnderstanding Environmental Contributions to Heterogeneity in bvFTD.P01AG066597 · NIA · UNIVERSITY OF PENNSYLVANIA · PI David John Irwin · 2020 to 2026
$18.8MGenetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4MAssessment of Candidate Loci in Neurological diseasesZIAAG000957 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$12.2MGenome wide SNP analysis in Amyotrophic Lateral SclerosisZIAAG000933 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$9.8MGenetic etiology of Fronto-Temporal Dementia, a dementia related to Alzheimers diseaseZIAAG000934 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$5.2MIdentification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6MBLRD VA I01 BX002466BLRD VA I01 BX005161Department of HealthIntramural NIH HHS ZIA AG000933Intramural NIH HHS ZIA AG000934Intramural NIH HHS ZIA AG000935Intramural NIH HHS ZIA NS003034Intramural NIH HHS ZIA NS003154Medical Research Council G0400074Medical Research Council G0600974Medical Research Council MC_EX_MR/M009203/1Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MC_PC_14089Medical Research Council MC_U105597119Medical Research Council MC_UU_00005/12Medical Research Council MR/L016397/1Medical Research Council MR/L501529/1Medical Research Council MR/M009203/1Medical Research Council MR/M024962/1Medical Research Council MR/N008324/1Medical Research Council MR/N026004/1Medical Research Council MR/R011354/1Medical Research Council MR/R024804/1Medical Research Council MR/S000992/1Medical Research Council MR/S006753/1Medical Research Council MR/T018569/1Motor Neurone Disease Association AL-CHALABI/APR15/844-791Motor Neurone Disease Association MCLAUGHLIN/OCT15/957-799Motor Neurone Disease Association TURNER/OCT18/989-797NIA NIH HHS K08 AG065463NIA NIH HHS P01 AG066597NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066514NINDS NIH HHS R01 NS073873NINDS NIH HHS R01 NS115144NINDS NIH HHS R56 NS073873Parkinson's UK J-0901Parkinson's UK K-1501Wellcome TrustWellcome Trust 103838
Abstract
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
Indexed as
DNA Repeat ExpansionAmyotrophic Lateral SclerosisFrontotemporal DementiaHumansHuntingtin ProteinMutationWhole Genome SequencingHTT protein, humanHuntingtin Proteinamyotrophic lateral sclerosisfrontotemporal dementiahuntingtinrepeat expansionswhole-genome sequencing
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.