Nat Neurosci. 2014 May;17(5):664-666. doi: 10.1038/nn.3688. Epub 2014 Mar 30.

Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.

Johnson JO^#¹, Pioro EP^#², Boehringer A^#³, Chia R^#⁴, Feit H⁵, Renton AE¹, Pliner HA¹, Abramzon Y¹, Marangi G^1,⁶, Winborn BJ⁷, Gibbs JR^8,⁹, Nalls MA¹⁰, Morgan S⁹, Shoai M⁹, Hardy J⁹, Pittman A⁹, Orrell RW¹¹, Malaspina A¹², Sidle KC⁹, Fratta P¹³, Harms MB¹⁴, Baloh RH¹⁵, Pestronk A¹⁴, Weihl CC¹⁴, Rogaeva E¹⁶, Zinman L¹⁷, Drory VE¹⁸, Borghero G¹⁹, Mora G²⁰, Calvo A²¹, Rothstein JD²²; ITALSGEN, Drepper C^23,²⁴, Sendtner M²³, Singleton AB¹⁰, Taylor JP⁷, Cookson MR⁴, Restagno G^#²⁵, Sabatelli M^#²⁶, Bowser R^#³, Chiò A^#²¹, Traynor BJ^#^1,²².

Author information

1: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
2: Department of Neurology, Neurological Institute, Neuromuscular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
3: Division of Neurology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ 85013, USA.
4: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
5: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA.
6: Institute of Medical Genetics, Catholic University of Sacred Heart, 10100 Rome, Italy.
7: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
8: Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
9: Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
10: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
11: Department of Clinical Neuroscience, Institute of Neurology, University College London, London NW3 2PG, UK.
12: Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, North-East London and Essex Regional MND Care Centre, E1 2AT, UK.
13: Department of Neurodegenerative Disease, University College London, Queen Square, London WC1N 3BG, UK.
14: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
15: Department of Neurology, Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA.
16: Tanz Centre for Research of Neurodegenerative Diseases, Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, M5S 3H2, Canada.
17: Division of Neurology, Department of Internal Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada.
18: Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
19: Department of Neurology, Azienda Universitaria-Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
20: ALS Center, Salvatore Maugeri Foundation, Milan, Italy.
21: 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, 10126 Turin, Italy.
22: Brain Science Institute and Department of Neurology, Johns Hopkins Hospital, 855 N. Wolfe Street, Baltimore, MD 21205, USA.
23: Institute for Clinical Neurobiology, University of Würzburg, D-97078 Würzburg, Germany.
24: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97080 Würzburg, Germany.
25: Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, 10126 Turin, Italy.
26: Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, 10100 Rome, Italy.
#: Contributed equally

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.