TBK1 is associated with ALS and ALS-FTD in Sardinian patients

Mario Sabatelli, Marcella Zollino, Giuseppe Marangi, Sandra D'Alfonso, Amelia Conte, Marco Luigetti, Serena Lattante, Giuseppe Borghero, Maura Pugliatti, Francesco Marrosu, Maria Giovanna Marrosu, Maria Rita Murru, Gianluca Floris, Antonino Cannas, Patrizia Occhineri, Tea B. Cau, Daniela Loi, Anna Ticca, Sebastiano Traccis, Umberto ManeraAntonio Canosa, Cristina Moglia, Andrea Calvo, Marco Barberis, Maura Brunetti, J. Raphael Gibbs, Alan E. Renton, Edoardo Errichiello, Magdalena Zoledziewska, Antonella Mulas, Yong Qian, Jun Din, Hannah A. Pliner, Bryan J. Traynor, Adriano Chiò, Francesco O. Logullo, Isabella Simone, Giancarlo Logroscino, Fabrizio Salvi, Ilaria Bartolomei, Margherita Capasso, Claudia Caponnetto, Paolo Mandich, Gianluigi Mancardi, Paola Origone, Francesca L. Conforti, Giuseppe Vita, Sonia Messina, Massimo Russo, Gabriele Mora, Kalliopi Marinou, Riccardo Sideri, Christian Lunetta, Silvana Penco, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Nilo Riva, Paola Carrera, Paolo Volanti, Lucio Tremolizzo, Carlo Ferrarese, Nicola Fini, Antonio Fasano, Maria Rosaria Monsurrò, Gioacchino Tedeschi, Francesca Trojsi, Giovanni Piccirillo, Viviana Cristillo, Letizia Mazzini, Anna Bersano, Lucia Corrado, Alessandra Bagarotti, Vincenzo La Bella, Rossella Spataro, Tiziana Colletti, Marialuisa Santarelli, Antonio Petrucci, Fabio Giannini, Stefania Battistini, Claudia Ricci, Michele Benigni, Gabriella Restagno, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Ilardi, Davide Bertuzzo, Raffaella Tanel, Fabrizio Pisano, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Angelo Pirisi, Leslie D. Parish, Enzo Ortu

Risultato della ricerca: Contributo in rivistaArticolo in rivista

23 Citazioni (Scopus)

Abstract

Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions.
Lingua originaleEnglish
pagine (da-a)180-180.e5
RivistaNeurobiology of Aging
Volume43
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Aging
  • Amyotrophic lateral sclerosis
  • Developmental Biology
  • Genetics
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Neuroscience (all)
  • Sporadic
  • TBK1

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