Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis

Tiloca, Cinzia; Ratti, Antonia; Pensato, Viviana; Castucci, Alessia; Sorarù, Gianni; Del Bo, Roberto; Corrado, Lucia; Cereda, Cristina; D'Ascenzo, Carla; Comi, Giacomo P.; Mazzini, Letizia; Castellotti, Barbara; Ticozzi, Nicola; Gellera, Cinzia; Silani, Vincenzo; SLAGEN Consortium,

doi:10.1016/j.neurobiolaging.2011.10.025

« Previous Next »Neurobiology of Aging
Volume 33, Issue 3 , Pages 630.e1-630.e2, March 2012

Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis

Cinzia Tiloca
- Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy
Antonia Ratti
- Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy
- Department of Neurological Sciences, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
Viviana Pensato
- Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
Alessia Castucci
- Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
Gianni Sorarù
- Department of Neurosciences, University of Padua, Padua, Italy
Roberto Del Bo
- Department of Neurological Sciences, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
- IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Lucia Corrado
- Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases, “A. Avogadro” University, Novara, Italy
Cristina Cereda
- Laboratory of Experimental Neurobiology, IRCCS, National Neurological Institute “C. Mondino,” Pavia, Italy
Carla D'Ascenzo
- Department of Neurosciences, University of Padua, Padua, Italy
Giacomo P. Comi
- Department of Neurological Sciences, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
- IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Letizia Mazzini
- Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy
Barbara Castellotti
- Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
Nicola Ticozzi
- Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy
Cinzia Gellera
- Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
- Co-senior authors.
Vincenzo Silani
- Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy
- Department of Neurological Sciences, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy
- Corresponding author at: Department of Neurology, IRCCS, Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy. Tel: +39 02 619112982; fax: +39 02 619112937
SLAGEN Consortium

Received 19 July 2011; accepted 23 October 2011. published online 05 December 2011.

Abstract

Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotide change (c.2814G>T) in the 3′ untranslated region (UTR). Bioinformatical analyses predicted no changes in splicing process or microRNA binding sites. Our results do not confirm a main contribution of VCP gene to familial ALS in the Italian population.

Keywords: ALS (Amyotrophic lateral sclerosis) , VCP (valosin-containing protein) , Genetics