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Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis.
Gang, Qiang; Bettencourt, Conceição; Machado, Pedro M; Brady, Stefen; Holton, Janice L; Pittman, Alan M; Hughes, Deborah; Healy, Estelle; Parton, Matthew; Hilton-Jones, David; Shieh, Perry B; Needham, Merrilee; Liang, Christina; Zanoteli, Edmar; de Camargo, Leonardo Valente; De Paepe, Boel; De Bleecker, Jan; Shaibani, Aziz; Ripolone, Michela; Violano, Raffaella; Moggio, Maurizio; Barohn, Richard J; Dimachkie, Mazen M; Mora, Marina; Mantegazza, Renato; Zanotti, Simona; Singleton, Andrew B; Hanna, Michael G; Houlden, Henry.
Afiliación
  • Gang Q; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK.
  • Bettencourt C; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London, UK.
  • Machado PM; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK; Centre for Rheumatology, Division of Medicine, University College Lon
  • Brady S; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
  • Holton JL; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK.
  • Pittman AM; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
  • Hughes D; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK.
  • Healy E; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK.
  • Parton M; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK.
  • Hilton-Jones D; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
  • Shieh PB; Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Needham M; Western Australian Neurosciences Research Institute (WANRI), University of Western Australia and Murdoch University, Fiona Stanley Hospital, Perth, Australia.
  • Liang C; Department of Neurology, Royal North Shore Hospital, New South Wales, Australia.
  • Zanoteli E; Department of Neurology, Medical School of the University of São Paulo (FMUSP), São Paulo, Brazil.
  • de Camargo LV; Department of Neurology, Medical School of the University of São Paulo (FMUSP), São Paulo, Brazil.
  • De Paepe B; Department of Neurology and Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium.
  • De Bleecker J; Department of Neurology and Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium.
  • Shaibani A; Nerve and Muscle Center of Texas, Houston, TX, USA.
  • Ripolone M; Neuromuscular Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, University of Milan, Milan, Italy.
  • Violano R; Neuromuscular Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, University of Milan, Milan, Italy.
  • Moggio M; Neuromuscular Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, University of Milan, Milan, Italy.
  • Barohn RJ; The University of Kansas Medical Centre, Kansas City, KS, USA.
  • Dimachkie MM; The University of Kansas Medical Centre, Kansas City, KS, USA.
  • Mora M; Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Isitituto Neurologico C. Besta, Milano, Italy.
  • Mantegazza R; Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Isitituto Neurologico C. Besta, Milano, Italy.
  • Zanotti S; Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Isitituto Neurologico C. Besta, Milano, Italy.
  • Singleton AB; Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD, USA.
  • Hanna MG; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK. Electronic address: m.hanna@ucl.ac.uk.
  • Houlden H; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK; Neurogenetics Laboratory, Institute of Neurology, University College
Neurobiol Aging ; 47: 218.e1-218.e9, 2016 11.
Article en En | MEDLINE | ID: mdl-27594680
Genetic factors have been suggested to be involved in the pathogenesis of sporadic inclusion body myositis (sIBM). Sequestosome 1 (SQSTM1) and valosin-containing protein (VCP) are 2 key genes associated with several neurodegenerative disorders but have yet to be thoroughly investigated in sIBM. A candidate gene analysis was conducted using whole-exome sequencing data from 181 sIBM patients, and whole-transcriptome expression analysis was performed in patients with genetic variants of interest. We identified 6 rare missense variants in the SQSTM1 and VCP in 7 sIBM patients (4.0%). Two variants, the SQSTM1 p.G194R and the VCP p.R159C, were significantly overrepresented in this sIBM cohort compared with controls. Five of these variants had been previously reported in patients with degenerative diseases. The messenger RNA levels of major histocompatibility complex genes were upregulated, this elevation being more pronounced in SQSTM1 patient group. We report for the first time potentially pathogenic SQSTM1 variants and expand the spectrum of VCP variants in sIBM. These data suggest that defects in neurodegenerative pathways may confer genetic susceptibility to sIBM and reinforce the mechanistic overlap in these neurodegenerative disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Adenosina Trifosfatasas / Proteínas de Ciclo Celular / Miositis por Cuerpos de Inclusión / Estudios de Asociación Genética / Proteína Sequestosoma-1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Neurobiol Aging Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Adenosina Trifosfatasas / Proteínas de Ciclo Celular / Miositis por Cuerpos de Inclusión / Estudios de Asociación Genética / Proteína Sequestosoma-1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Neurobiol Aging Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos