ArticleAmerican journal of human genetics2016
Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.
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Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 268 papers, 2 of them syntheses that pooled it.
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268citing papers in PubMed, 2 pooled it
28.3field-weighted citation impact, top 1% of its field
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Who cites it
268 citing papers in PubMed, 2 syntheses or guidelines pooled it, 434 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Mechanisms and Therapeutic Potential of Targeting Mitophagy in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Parkinson's disease-associatedeLife · 2026Article
- Co- and Multi-Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.Molecular cell · 2026Article
- Adult-Onset SCAR4 with a 30-Year Slowly Progressive Course: First Combined Assessment with FDG-PET and Brain Perfusion SPECT.Cerebellum (London, England) · 2026Review
- Neuropathology in genetic Parkinson's disease: a focused review of pathological and clinical findings.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Advances and challenges of splicing prediction with AI.Nature genetics · 2026Review
- Landscape of copy number variants in Spanish people with dementia.NPJ genomic medicine · 2026Article
- Structural Mechanism and Cellular Restriction of Tau Seeding from Endolysosomes.bioRxiv : the preprint server for biology · 2026Article
- A genome-wide association study of young onset Parkinson's disease in European ancestry.medRxiv : the preprint server for health sciences · 2026Article
- Allele specific expression in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The vicious cycle: unraveling the interplay between α-synuclein, mitochondrial dysfunction, and neuroinflammation in Parkinson's disease.Journal of neurology · 2026Review
- Four subtypes of disease-causing missense mutations underlie pathogenic protein interactions in neurodegenerative VPS13A disease.The Journal of clinical investigation · 2026Article
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis.The Journal of cell biology · 2026Article
- VPS13 has an important role in female germline development in Arabidopsis.The Plant journal : for cell and molecular biology · 2026Article
208 more citing papers are in PubMed but not listed here.
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Authors and funding
44 authors at 16 institutions in 6 countries.
Suzanne LesageSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Valérie DrouetSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Elisa MajounieLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Vincent DeramecourtDepartment of Histology and Pathology, University of Lille Nord de France, Lille University Hospital, 59000 Lille, France.
Maxime JacoupySorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Aude NicolasSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Florence Cormier-DequaireSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France; Centre d'Investigation Clinique Pitié Neurosciences CIC-1422, 75013 Paris, France.
Sidi Mohamed HassounSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Claire PujolSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Sorana CiuraSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Zoi ErpapazoglouSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Tatiana UsenkoSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Claude-Alain MaurageDepartment of Histology and Pathology, University of Lille Nord de France, Lille University Hospital, 59000 Lille, France.
Mourad SahbatouFondation Jean Dausset-CEPH, 75010 Paris, France.
Stefan LiebauInstitute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany.
Jinhui DingLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Basar BilgicBehavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey.
Murat EmreBehavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey.
Nihan Erginel-UnaltunaDepartment of Genetics, Institute for Experimental Medicine, Istanbul University, 34390 Istanbul, Turkey.
Gamze GuvenDepartment of Genetics, Institute for Experimental Medicine, Istanbul University, 34390 Istanbul, Turkey.
François TisonInstitut des Maladies Neurodégénératives, Université de Bordeaux et CHU de Bordeaux, 33000 Bordeaux, France.
Christine TranchantPôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, 67000 Strasbourg, France.
Marie VidailhetSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France; Pôle des Maladies du Système Nerveux, Fédération de Neurologie, Hôpital de la Salpêtrière, 75013 Paris, France.
Jean-Christophe CorvolSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France; Centre d'Investigation Clinique Pitié Neurosciences CIC-1422, 75013 Paris, France.
Paul KrackNeurology Department, CHU de Grenoble, Joseph Fourier University, and INSERM U836, 38000 Grenoble, France.
Anne-Louise LeuteneggerInserm U946, 75010 Paris, France; Université Paris Diderot, Institut Universitaire d'Hématologie, UMR946, 75010 Paris, France.
Michael A NallsLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Peter HeutinkHertie Institute for Clinical Brain Research, University of Tübingen and DZNE, German Center for Neurodegenerative Diseases, 72074 Tübingen, Germany.
J Raphael GibbsLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
John HardyDepartment of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
Nicholas W WoodDepartment of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
Thomas GasserHertie Institute for Clinical Brain Research, University of Tübingen and DZNE, German Center for Neurodegenerative Diseases, 72074 Tübingen, Germany.
Alexandra DurrSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France; Department of Genetics and Cytogenetics, AP-HP, Hôpital de la Salpêtrière, 75013 Paris, France.
Jean-François DeleuzeCommissariat à l'Energie Atomique, Institut Génomique, Centre National de Génotypage, 91000 Evry, France.
Meriem TazirService de Neurologie CHU Mustapha, 16000 Alger, Algérie.
Alain DestéeMovement Disorders Unit, Lille University, Inserm U837, Lille University Hospital, 59000 Lille, France.
Ebba LohmannBehavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey; Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, 72076 Tübingen, Germany.
Edor KabashiSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France.
Andrew SingletonLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Olga CortiSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France. Electronic address: olga.corti@upmc.fr.
Alexis BriceSorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France; Inserm U 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France; Department of Genetics and Cytogenetics, AP-HP, Hôpital de la Salpêtrière, 75013 Paris, France. Electronic address: alexis.brice@upmc.fr.
French Parkinson's Disease Genetics Study (PDG)
International Parkinson's Disease Genomics Consortium (IPDGC)
Centre National de la Recherche Scientifique · FRNational Institute on Aging · USGerman Center for Neurodegenerative Diseases · DEInserm · FRHertie Institute for Clinical Brain Research · DEIstanbul University · TRUniversité de Bordeaux · FRHospices Civils de Lyon · FRCentre National de Recherche en Génomique Humaine · FRNational Hospital for Neurology and Neurosurgery · GBUniversité Lille Nord de France · FRUniversity College London · GBCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRFondation Jean Dausset-CEPH · FRHôpital Mustapha Pacha · DZUniversity of Tübingen · DE
Funding
Genetic analysis in families with neurological diseaseZIAAG000958 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$10.9MINVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASER01NS075321 · NINDS · WASHINGTON UNIVERSITY · PI CAMPBELL, MEGHAN C, PERLMUTTER, JOEL SYNES · 2011 to 2021
$8.2MWhole Genome Screen in families with Parkinson's diseaseZ01AG000958 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2003 to 2008
$1.4MIntramural NIH HHS Z01 AG000958Medical Research Council G0700943Medical Research Council G1100643Medical Research Council G1100643/1Medical Research Council MR/L501554/1NINDS NIH HHS R01 NS075321Parkinson's UK F-1202Parkinson's UK G-0909Parkinson's UK G-1107Parkinson's UK K-1501
Abstract
Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression.
Indexed as
AdultAgedAnimalsCase-Control StudiesConsanguinityCOS CellsFemaleGene SilencingGenetic HeterogeneityHEK293 CellsHeterozygoteHomozygoteHumansMaleMiddle AgedMitophagyparkin proteinProtein KinasesProteinsPTEN-Induced Putative KinaseUbiquitin-Protein LigasesVPS13C protein, human
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