Evidence map›Paper›PMID 39677454›Full record

ArticlemedRxiv : the preprint server for health sciences2024

Genetic Diversity and Expanded Phenotypes in Dystonia: Insights from Large-Scale Exome Sequencing.

Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker and 37 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors.

Mirja ThomsenInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Fabian OttMedical Systems Biology Division, Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany.
Sebastian LoensInstitute of Systems Motor Science, University of Lübeck, 23538 Lübeck, Germany.
Gamze Kilic-BerkmenDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA.
Ai Huey TanDivision of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Shen-Yang LimDivision of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Ebba LohmannHertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE)-Tübingen, 72076 Tübingen, Germany.
Kaja M SchröderInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Lea IpsenInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Lena A NothackerInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Linn WelzelInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Alexandra S RudnikInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Frauke HinrichsInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Thorsten OdorferDepartment of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
Kirsten E ZeunerDepartment of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Friederike SchumannDepartment of Neurology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Andrea A KühnDepartment of Neurology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Simone ZittelDepartment of Neurology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Marius MoellerMedical Systems Biology Division, Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany.
Robert PfisterNeurological Practice, 86356 Neusäß, Germany.
Christoph KammDepartment of Neurology, University Medical Center Rostock, 18057 Rostock, Germany.
Anthony E LangEdmond J. Safra Program in Parkinson's Disease, the Rossy PSP Centre and Department of Medicine (Neurology), Toronto Western Hospital, University of Toronto, Toronto, ON M5T 2S8, Canada.ORCID 0000-0003-1229-3667
Yi Wen TayDivision of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Marie VidailhetSorbonne University, Paris Brain Institute (ICM), Inserm, CNRS, and Center of Excellence of Neurodegenerative Disease (CoEN), AP-HP, Pitié-Salpêtrière Hospital, 75013 Paris, France.
Emmanuel RozeSorbonne University, Paris Brain Institute (ICM), Inserm, CNRS, and Center of Excellence of Neurodegenerative Disease (CoEN), AP-HP, Pitié-Salpêtrière Hospital, 75013 Paris, France.
Joel S PerlmutterDepartments of Neurology, Radiology and Neuroscience, Washington University, St. Louis, MO 63110, USA.
Jeanne S FeuersteinDepartment of Neurology, University of Colorado, Aurora, CO 80045, USA.
Victor S C FungMovement Disorders Unit, Department of Neurology, Westmead Hospital & Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia.
Florence ChangMovement Disorders Unit, Department of Neurology, Westmead Hospital & Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia.
Richard L BarbanoDepartment of Neurology, University of Rochester, Rochester, NY 14627, US.
Steven BellowsBaylor College of Medicine, Department of Neurology, Houston, TX 77030, US.
Aparna A Wagle ShuklaDepartment of Neurology, University of Florida, Gainesville, FL 32611, USA.
Alberto J EspayJames J and Joan A Gardner Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH 45219, USA.
Mark S LeDouxDepartment of Psychology, University of Memphis, Memphis, TN 38152, USA AND Veracity Neuroscience LLC, Memphis, TN 38157, USA.
Brian D BermanDepartment of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-0602-9942
Stephen ReichNeurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Andres DeikDepartment of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-Universität and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Michael WittigInstitute of Clinical Molecular Biology, Christian-Albrechts-Universität and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Sören FranzenburgInstitute of Clinical Molecular Biology, Christian-Albrechts-Universität and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Jens VolkmannDepartment of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
Norbert BrüggemannInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
H A JinnahDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA.
Tobias BäumerInstitute of Systems Motor Science, University of Lübeck, 23538 Lübeck, Germany.
Christine KleinInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.
Hauke BuschMedical Systems Biology Division, Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany.ORCID 0000-0003-4763-4521
Katja LohmannInstitute of Neurogenetics, University of Lübeck, 23538 Lübeck, Germany.

Funding

Medicinal Chemistry CoreU19NS110456 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ROBERT H MACH · 2019 to 2026
$44.1M
Dystonia Coalition- Pilot ProjectU54NS116025 · NINDS · EMORY UNIVERSITY · PI JINNAH, HYDER A · 2019 to 2023
$7.1M
Dystonia CoalitionU54NS065701 · NINDS · EMORY UNIVERSITY · PI JINNAH, HYDER A · 2009 to 2014
$7.0M
Protein Aggregation and Neurotransmitter Deficits in Parkinson DiseaseR01NS097799 · NINDS · WASHINGTON UNIVERSITY · PI PAUL T KOTZBAUER · 2016 to 2026
$5.8M
Parkinson Disease Clinical Subtypes: Validation, Clinical Utility, and Biological CorrelatesR01NS097437 · NINDS · WASHINGTON UNIVERSITY · PI MEGHAN C CAMPBELL · 2017 to 2026
$4.1M
Neuroinflammatory Biomarkers for Nigrostriatal InjuryR01NS107281 · NINDS · WASHINGTON UNIVERSITY · PI PERLMUTTER, JOEL SYNES · 2019 to 2023
$3.3M
Multi-tissue High-throughput Proteomic and Genomic Study in Parkinson's DiseaseR01NS118146 · NINDS · WASHINGTON UNIVERSITY · PI BENITEZ, BRUNO · 2020 to 2025
$3.2M
Neuroimaging of PDE10AR01NS103957 · NINDS · WASHINGTON UNIVERSITY · PI PERLMUTTER, JOEL SYNES, TU, ZHUDE · 2017 to 2021
$3.1M
The Role of Striatal Cholinergic Interneurons in DystoniaR01NS124789 · NINDS · WASHINGTON UNIVERSITY · PI Scott Allen Norris · 2022 to 2026
$3.0M
CARBOXYFULLERENE TREATMENT OF MPTP-INDUCED PARKINSONISMR01NS050425 · NINDS · WASHINGTON UNIVERSITY · PI PERLMUTTER, JOEL SYNES · 2005 to 2009
$2.6M
Dystonia CoalitionU54TR001456 · NCATS · EMORY UNIVERSITY · PI JINNAH, HYDER A · 2015 to 2016
$2.5M
Prospective memory impairment in Parkinson disease-related cognitive decline: Intervention and mechanismsR01AG065214 · NIA · WASHINGTON UNIVERSITY · PI FOSTER, ERIN · 2020 to 2024
$2.5M
NCATS NIH HHS R21 TR004422NCATS NIH HHS R21 TR005231NCATS NIH HHS U54 TR001456NCCIH NIH HHS R33 AT010753NCRR NIH HHS C06 RR020092NIA NIH HHS R01 AG065214NINDS NIH HHS R01 NS050425NINDS NIH HHS R01 NS097437NINDS NIH HHS R01 NS097799NINDS NIH HHS R01 NS103957NINDS NIH HHS R01 NS107281NINDS NIH HHS R01 NS118146NINDS NIH HHS R01 NS124738NINDS NIH HHS R01 NS124789NINDS NIH HHS R01 NS134586NINDS NIH HHS R21 NS133875NINDS NIH HHS RF1 NS075321NINDS NIH HHS U19 NS110456NINDS NIH HHS U54 NS065701NINDS NIH HHS U54 NS116025
6 · The paper itself

Abstract

Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and genetic variants has become increasingly complex. To comprehensively unravel dystonia's genetic spectrum, we performed exome sequencing on 1,924 dystonia patients [40.3% male, 92.9% White, 93.2% isolated dystonia, median age at onset (AAO) 33 years], including 1,895 index patients, who were previously genetically unsolved. The sample was mainly based on two dystonia registries (DysTract and the Dystonia Coalition). Further, 72 additional patients of Asian ethnicity, mainly from Malaysia, were also included. We prioritized patients with negative genetic prescreening, early AAO, positive family history, and multisite involvement of dystonia. Rare variants in genes previously linked to dystonia (

Indexed as

DystoniaExome sequencingGenetic heterogeneityPathogenic variants

Identifiers

PMID39677454
PMCPMC11643126

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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.