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Genetic analysis of neurodegenerative diseases in a pathology cohort.
Blauwendraat, Cornelis; Pletnikova, Olga; Geiger, Joshua T; Murphy, Natalie A; Abramzon, Yevgeniya; Rudow, Gay; Mamais, Adamantios; Sabir, Marya S; Crain, Barbara; Ahmed, Sarah; Rosenthal, Liana S; Bakker, Catherine C; Faghri, Faraz; Chia, Ruth; Ding, Jinhui; Dawson, Ted M; Pantelyat, Alexander; Albert, Marilyn S; Nalls, Mike A; Resnick, Susan M; Ferrucci, Luigi; Cookson, Mark R; Hillis, Argye E; Troncoso, Juan C; Scholz, Sonja W.
Affiliation
  • Blauwendraat C; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Pletnikova O; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Geiger JT; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Murphy NA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Abramzon Y; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Molecular Neuroscience, University College London, London, UK.
  • Rudow G; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mamais A; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Sabir MS; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Crain B; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ahmed S; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Rosenthal LS; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bakker CC; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Faghri F; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Chia R; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Ding J; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Dawson TM; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Solomon H. Synder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Neu
  • Pantelyat A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Albert MS; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Nalls MA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
  • Resnick SM; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
  • Ferrucci L; Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
  • Cookson MR; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Hillis AE; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Troncoso JC; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Scholz SW; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sonja.scholz@nih.gov.
Neurobiol Aging ; 76: 214.e1-214.e9, 2019 04.
Article in En | MEDLINE | ID: mdl-30528841
ABSTRACT
Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations.
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Full text: 1 Database: MEDLINE Main subject: Neurodegenerative Diseases / Genetic Association Studies / High-Throughput Screening Assays / Mutation Type of study: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Year: 2019 Type: Article
Fulltext
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Full text: 1 Database: MEDLINE Main subject: Neurodegenerative Diseases / Genetic Association Studies / High-Throughput Screening Assays / Mutation Type of study: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Year: 2019 Type: Article