ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Mario Sabatelli, Adriano Chiò, Gabriele Mora, Claudia Caponnetto, Christian Lunetta, Bryan J. Traynor, Janel O. Johnson, Mike A. Nalls, Andrea Calvo, Cristina Moglia, Giuseppe Borghero, Francesca Trojsi, Vincenzo La Bella, Paolo Volanti, Isabella Simone, Fabrizio Salvi, Francesco O. Logullo, Nilo Riva, Paola Carrera, Fabio GianniniJessica Mandrioli, Raffaella Tanel, Margherita Capasso, Lucio Tremolizzo, Stefania Battistini, Maria Rita Murru, Paola Origone, Silvana Penco, Letizia Mazzini, Sandra D'Alfonso, Gabriella Restagno, Maura Brunetti, Marco Barberis, Francesca L. Conforti, Giancarlo Logroscino, Ilaria Bartolomei, Gianluigi Mancardi, Paola Mandich, Kalliopi Marinou, Riccardo Sideri, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Nicola Fini, Antonio Fasano, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Bersano, Lucia Corrado, Alessandra Bagarotti, Rossella Spataro, Tiziana Colletti, Marialuisa Santarelli, Antonio Petrucci, Claudia Ricci, Michele Benigni, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Ilardi, Umberto Manera, 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, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Stefania Cuccu, Stefania Tranquilli, Anna Ticca, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Enzo Ortu, Tea B. Cau, Daniela Loi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)

Abstract

There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients.
Lingua originaleEnglish
pagine (da-a)e5-e8
RivistaNeurobiology of Aging
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • ATXN2
  • Amyotrophic lateral sclerosis
  • C9ORF72
  • Phenotype

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