ArticleCell2018
Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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139citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% of its field
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.
- Decoding the Alphabet Soup: A Practical Guide to Genetic Testing in Hyperkinetic Movement Disorders.Tremor and other hyperkinetic movements (New York, N.Y.) · 2025Pooled it
- Founder mutations in movement disorders: global distribution, molecular mechanisms, and clinical consequences-a scoping review.Neurogenetics · 2026Article
- Regional and Compartmental Changes Drive Progressive Patterns of Striatal Degeneration in X-Linked Dystonia Parkinsonism.Annals of neurology · 2026Article
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Multiplatform single-cell and spatial transcriptomics reveal sex-specific malignant states and architecture in male breast cancer.Science advances · 2026Article
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- Mitochondrial toxins cause widespread downregulation of pathways in X-linked dystonia-parkinsonism patient-derived neurons.Stem cell reports · 2026Article
- Striatal hyperechogenicity as an ultrasound imaging marker for prodromal X-linked dystonia-parkinsonism.NPJ Parkinson's disease · 2026Article
- Correction of the molecular phenotype of X-linked Dystonia-Parkinsonism reveals a non-canonical function of BRD4.Nature communications · 2026Article
- TAF1 aggravates ferroptosis by promoting the ubiquitin-mediated degradation of nuclear GPX4.Journal of Zhejiang University. Science. B · 2026Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- A Modular DNAzyme for Precise Visualization and Intervention of Alternative Splicing Isoforms in Live Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism.American journal of human genetics · 2026Article
- Infantile Epileptic Spasm Syndrome Caused byHuman mutation · 2026Article
- Long-read sequencing identifies a novel de novo inversion in SMARCC2 in a pediatric patient with Coffin-siris syndrome 8: a case report.BMC medical genomics · 2025Article
- FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?Brain : a journal of neurology · 2025Article
- Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.medRxiv : the preprint server for health sciences · 2025Article
- Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism.bioRxiv : the preprint server for biology · 2025Article
- Hidden SVA retrotransposon insertion in BRCA1 revealed by nanopore targeted sequencing causes hereditary breast and ovarian cancer.Journal of human genetics · 2025Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
45 authors at 13 institutions in 3 countries.
Tatsiana AneichykCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.
William T HendriksDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Rachita YadavCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.
David ShinDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Dadi GaoCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.
Christine A VaineDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Ryan L CollinsCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.
Aloysius DomingoCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Benjamin CurrallCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Alexei StortchevoiCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Trisha Multhaupt-BuellDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Ellen B PenneyDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Lilian CruzDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Jyotsna DhakalDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Harrison BrandCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Carrie HanscomCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Caroline AntolikCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Marisela DyDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Ashok RagavendranCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jason UnderwoodPacific Biosciences, Menlo Park, CA 94025, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Stuart CantsilierisDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Katherine M MunsonDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Patrick AcuñaDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Criscely GoJose Reyes Memorial Medical Center, Manila, Philippines.
R Dominic G JamoraPhilippine General Hospital, Manila, Philippines.
Raymond L RosalesUniversity of Santo Tomas Hospital, Manila, Philippines.
Deanna M Church10X Genomics, Pleasanton, CA 94566, USA.
Stephen R Williams10X Genomics, Pleasanton, CA 94566, USA.
Sarah Garcia10X Genomics, Pleasanton, CA 94566, USA.
Christine KleinInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Ulrich MüllerInstitut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
Kirk C WilhelmsenUniversity of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
H T Marc TimmersGerman Cancer Consortium (DKTK) partner site Freiburg and Department of Urology, University Medical Center, Freiburg, Germany.
Yechiam SapirDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Brian J WaingerDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Daniel HendersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Naoto ItoDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Neil Weisenfeld10X Genomics, Pleasanton, CA 94566, USA; Genome Sequencing and Analysis Program, Broad Institute, Cambridge, MA 02142, USA.
David Jaffe10X Genomics, Pleasanton, CA 94566, USA; Genome Sequencing and Analysis Program, Broad Institute, Cambridge, MA 02142, USA.
Nutan SharmaDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Xandra O BreakefieldDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Laurie J OzeliusDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
D Cristopher BraggDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA. Electronic address: bragg@helix.mgh.harvard.edu.
Michael E TalkowskiCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA; Departments of Psychiatry and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: mtalkowski@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · US10X Genomics (United States) · USBroad Institute · USUniversity of Washington · USHoward Hughes Medical Institute · USJosé R. Reyes Memorial Medical Center · PHPhilippine General Hospital · PHUniversity Medical Center Freiburg · DEUniversity of Giessen · DEUniversity of Lübeck · DEUniversity of North Carolina at Chapel Hill · USUniversity of Santo Tomas Hospital · PH
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MClinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2MTorsinA as a key link in receptor-mediated signalingP01NS087997 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, OZELIUS, LAURIE J. · 2015 to 2019
$6.4MAssembling the Genetic Architecture of X-linked Dystonia ParkinsonismR01NS102423 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI David Cristopher Bragg, Clotilde Lagier-Tourenne · 2017 to 2026
$5.4MInflux Flow CytometerS10OD016372 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2013 to 2013
$600kImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595kTranslational Immunology Core's FACSAria Cell SorterS10RR023440 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2008 to 2008
$500kDEPARTMENT OF PATHOLOGY LSR2 CYTOMETER: TRANSPLANTATIONS10RR020936 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2005 to 2005
$389kHoward Hughes Medical InstituteNCRR NIH HHS S10 RR020936NCRR NIH HHS S10 RR023440NHGRI NIH HHS UM1 HG008900NICHD NIH HHS R01 HD081256NIH HHS S10 OD012027NIH HHS S10 OD016372NINDS NIH HHS P01 NS087997NINDS NIH HHS R01 NS102423
Abstract
X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.
Indexed as
Genome, HumanAlternative SplicingAlu ElementsBase SequenceCohort StudiesCRISPR-Cas SystemsDystonic DisordersFamilyFemaleGenetic Diseases, X-LinkedGenetic LociHaplotypesHigh-Throughput Nucleotide SequencingHistone AcetyltransferasesHumansInduced Pluripotent Stem CellsHistone AcetyltransferasesRNA, MessengerTATA-binding protein associated factor 250 kDaTATA-Binding Protein Associated FactorsTranscription Factor TFIIDdystoniaDYT3genome assemblyintron retentionParkinson’s diseaseretrotransposonSVATAF1transcriptome assemblyXDP
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