FUS mutations in sporadic amyotrophic lateral sclerosis

Lai, Shiao-Lin; Abramzon, Yevgeniya; Schymick, Jennifer C.; Stephan, Dietrich A.; Dunckley, Travis; Dillman, Allissa; Cookson, Mark; Calvo, Andrea; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; Spataro, Rossella; Monsurro, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Lombardo, Federica; the ITALSGEN Consortium,; Mora, Gabriele; Restagno, Gabriella; Chiò, Adriano; Traynor, Bryan J.

doi:10.1016/j.neurobiolaging.2009.12.020

« Previous Next »Neurobiology of Aging
Volume 32, Issue 3 , Pages 550.e1-550.e4, March 2011

FUS mutations in sporadic amyotrophic lateral sclerosis

Shiao-Lin Lai
- Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
- Department of Molecular Neuroscience and Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, Queen Square, London WC1 3BG, UK
- Chang Gung University College of Medicine and Hospital, Chiayi, Taiwan
- These authors contributed equally to this work.
Yevgeniya Abramzon
- Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
- These authors contributed equally to this work.
Jennifer C. Schymick
- Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
- Department of Clinical Medicine, University of Oxford, Oxford OX1 3QX, UK
Dietrich A. Stephan
- Navigenics, Foster City, CA 94404, USA
- IGNITE Institute for Individualized Health, Fairfax, VA 22042, USA
Travis Dunckley
- Neurogenomics Division, Translational Genomics Institute (TGEN), Phoenix, AZ 85004, USA
Allissa Dillman
- Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
Mark Cookson
- Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
Andrea Calvo
- Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy
Stefania Battistini
- Department of Neuroscience, Neurology Section, University of Siena, Siena, Italy
Fabio Giannini
- Department of Neuroscience, Neurology Section, University of Siena, Siena, Italy
Claudia Caponnetto
- Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Giovanni Luigi Mancardi
- Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Rossella Spataro
- Department of Clinical Neurosciences, University of Palermo, Italy
Maria Rosaria Monsurro
- Department of Neuroscience, Second University of Naples, Naples, Italy
- Capodimonte-Hermitage Institute, Naples, Italy
Gioacchino Tedeschi
- Department of Neuroscience, Second University of Naples, Naples, Italy
- Capodimonte-Hermitage Institute, Naples, Italy
Kalliopi Marinou
- Fondazione Salvatore Maugeri, Milan, Italy
Mario Sabatelli
- Neurological Institute, Catholic University and I.CO.M.M. Association for ALS Research, Rome, Italy
Amelia Conte
- Neurological Institute, Catholic University and I.CO.M.M. Association for ALS Research, Rome, Italy
Jessica Mandrioli
- Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena, Modena, Italy
Patrizia Sola
- Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena, Modena, Italy
Fabrizio Salvi
- Department of Neurology, Center for Diagnosis and Cure of Rare Diseases, Bellaria Hospital, Bologna, Italy
Ilaria Bartolomei
- Department of Neurology, Center for Diagnosis and Cure of Rare Diseases, Bellaria Hospital, Bologna, Italy
Federica Lombardo
- Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, Turin, Italy
the ITALSGEN Consortium
- See Appendix A for the other members of ITALSGEN.
Gabriele Mora
- Fondazione Salvatore Maugeri, Milan, Italy
Gabriella Restagno
- Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, Turin, Italy
- These authors contributed equally to this work.
Adriano Chiò
- Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy
- These authors contributed equally to this work.
Bryan J. Traynor
- Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
- These authors contributed equally to this work.
- Corresponding author at: Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, NIA, National Institutes of Health, 35 Convent Drive, Room 1A-1000, Bethesda, MD 20892, USA. Tel.: +1 301 451 7606; fax: +1 301 451 7295.

Received 2 September 2009; received in revised form 8 December 2009; accepted 24 December 2009. published online 08 February 2010.

Abstract

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease.

Keywords: Amyotrophic lateral sclerosis, Sporadic disease, FUS, Italy, United States of America