title: Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vance
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Boris
authors.initials: B
authors.lastname: Rogelj
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobágyi
authors.affiliation: Department of Neuroscience, King's College London, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: De Vos
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Agnes Lumi
authors.initials: AL
authors.lastname: Nishimura
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Jemeen
authors.initials: J
authors.lastname: Sreedharan
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Bradley
authors.initials: B
authors.lastname: Smith
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ruddy
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Wright
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Jeban
authors.initials: J
authors.lastname: Ganesalingam
authors.affiliation: Northcott Neuroscience Laboratory, Australian and New Zealand Army Corps (ANZAC) Research Institute, Concord, NSW 2139, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Tripathi
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Saraj
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: P Nigel
authors.initials: PN
authors.lastname: Leigh
authors.affiliation: Northcott Neuroscience Laboratory, Australian and New Zealand Army Corps (ANZAC) Research Institute, Concord, NSW 2139, Australia.|Faculty of Medicine, University of Sydney, Sydney, NSW 2139, Australia.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Blair
authors.affiliation: Northcott Neuroscience Laboratory, Australian and New Zealand Army Corps (ANZAC) Research Institute, Concord, NSW 2139, Australia.|Molecular Medicine Laboratory, Concord Hospital, Concord, NSW 2139, Australia.|Faculty of Medicine, University of Sydney, Sydney, NSW 2139, Australia.
authors.forename: Garth
authors.initials: G
authors.lastname: Nicholson
authors.affiliation: Division of Neurosciences and Mental Health, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: de Belleroche
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gallo
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.|Department of Neuroscience, King's College London, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Miller
authors.affiliation: Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Shaw
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D034702:RNA-Binding Protein FUS / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000473:pathology; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D034702:RNA-Binding Protein FUS