Contributors: Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Lunetta, Christian; Traynor, Bryan J.; Johnson, Janel O.; Nalls, Mike A.; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Trojsi, Francesca; La Bella, Vincenzo; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O.; Riva, Nilo; Carrera, Paola; Giannini, Fabio; Mandrioli, Jessica; Tanel, Raffaella; Capasso, Margherita; Tremolizzo, Lucio; Battistini, Stefania; Murru, Maria Rita; Origone, Paola; Zollino, Marcella; Penco, Silvana; Mazzini, Letizia; D'Alfonso, Sandra; Restagno, Gabriella; Brunetti, Maura; Barberis, Marco; Conforti, Francesca L.; Logroscino, Giancarlo; Bartolomei, Ilaria; Mancardi, Gianluigi; Mandich, Paola; Marinou, Kalliopi; Sideri, Riccardo; Mosca, Lorena; Lauria Pinter, Giuseppe; Corbo, Massimo; Fini, Nicola; Fasano, Antonio; Arosio, Alessandro; Ferrarese, Carlo; Tedeschi, Gioacchino; Monsurrò, Maria Rosaria; Piccirillo, Giovanni; Femiano, Cinzia; Bersano, Anna; Corrado, Lucia; Bagarotti, Alessandra; Spataro, Rossella; Colletti, Tiziana; Conte, Amelia; Luigetti, Marco; Lattante, Serena; Marangi, Giuseppe; Santarelli, Marialuisa; Petrucci, Antonio; Ricci, Claudia; Benigni, Michele; Casale, Federico; Marrali, Giuseppe; Fuda, Giuseppe; Ossola, Irene; Cammarosano, Stefania; Ilardi, Antonio; Manera, Umberto; Bertuzzo, Davide; Pisano, Fabrizio; Costantino, Emanuela; Pani, Carla; Puddu, Roberta; Caredda, Carla; Piras, Valeria; Tranquilli, Stefania; Cuccu, Stefania; Corongiu, Daniela; Melis, Maurizio; Milia, Antonio; Marrosu, Francesco; Marrosu, Maria Giovanna; Floris, Gianluca; Cannas, Antonino; Ticca, Anna; Pugliatti, Maura; Pirisi, Angelo; Parish, Leslie D.; Occhineri, Patrizia; Ortu, Enzo; Cau, Tea B.; Loi, Daniela
نبذة مختصرة : 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 ¼ 0.137; Sardinian cases, p ¼ 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p ¼ 0.005; Sardinian cases, p ¼ 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.
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