FUS mutations in sporadic amyotrophic lateral sclerosis

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

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

a Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA

b Department of Molecular Neuroscience and Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, Queen Square, London WC1 3BG, UK

c Chang Gung University College of Medicine, Taiwan

d Department of Clinical Medicine, University of Oxford, Oxford OX1 3QX, UK

e Navigenics, Foster City, CA 94404, USA

f IGNITE Institute for Individualized Health, Fairfax, VA 22042, USA

g Neurogenomics Division, Translational Genomics Institute (TGEN), Phoenix, AZ 85004, USA

h Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA

i Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy

j Department of Neuroscience, Neurology Section, University of Siena, Siena, Italy

k Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy

l Department of Clinical Neurosciences, University of Palermo, Italy

m Department of Neuroscience, Second University of Naples, Naples, Italy

n Capodimonte-Hermitage Institute, Naples, Italy

o Fondazione Salvatore Maugeri, Milan, Italy

p Neurological Institute, Catholic University and I.CO.M.M. Association for ALS Research, Rome, Italy

q Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena, Modena, Italy

r Department of Neurology, Center for Diagnosis and Cure of Rare Diseases, Bellaria Hospital, Bologna, Italy

s Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, Turin, Italy

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.

1 These authors contributed equally to this work.

2 See Appendix A for the other members of ITALSGEN.

PII: S0197-4580(10)00005-9

doi:10.1016/j.neurobiolaging.2009.12.020

Published by Elsevier Inc.

*Note: Add-ons open in a new browser window. Please disable any pop-up blocking software before viewing Add-ons.