title: Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
abstract: MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration.
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.affiliation: Department of Neurology, Neurological Institute, Neuromuscular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Pioro
authors.affiliation: Division of Neurology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ 85013, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Boehringer
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Chia
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Feit
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Renton
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Pliner
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Abramzon
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.|Institute of Medical Genetics, Catholic University of Sacred Heart, 10100 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Winborn
authors.affiliation: Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.|Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shoai
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Pittman
authors.affiliation: Department of Clinical Neuroscience, Institute of Neurology, University College London, London NW3 2PG, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Orrell
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, North-East London and Essex Regional MND Care Centre, E1 2AT, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.affiliation: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Katie C
authors.initials: KC
authors.lastname: Sidle
authors.affiliation: Department of Neurodegenerative Disease, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Harms
authors.affiliation: Department of Neurology, Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Baloh
authors.affiliation: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.affiliation: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Conrad C
authors.initials: CC
authors.lastname: Weihl
authors.affiliation: Tanz Centre for Research of Neurodegenerative Diseases, Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, M5S 3H2, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.affiliation: Division of Neurology, Department of Internal Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada.
authors.forename: Lorne
authors.initials: L
authors.lastname: Zinman
authors.affiliation: Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Vivian E
authors.initials: VE
authors.lastname: Drory
authors.affiliation: Department of Neurology, Azienda Universitaria-Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.affiliation: ALS Center, Salvatore Maugeri Foundation, Milan, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, 10126 Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: Brain Science Institute and Department of Neurology, Johns Hopkins Hospital, 855 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rothstein
authors.affiliation: Institute for Clinical Neurobiology, University of Würzburg, D-97078 Würzburg, Germany.|Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Drepper
authors.affiliation: Institute for Clinical Neurobiology, University of Würzburg, D-97078 Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Taylor
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.affiliation: Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, 10126 Turin, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.affiliation: Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, 10100 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
authors.affiliation: Division of Neurology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ 85013, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, 10126 Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.|Brain Science Institute and Department of Neurology, Johns Hopkins Hospital, 855 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins