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.
Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Lunetta, C., Traynor, B., et al. (2016). ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion. NEUROBIOLOGY OF AGING, 39, 218-218.e8 [10.1016/j.neurobiolaging.2015.11.027].
|Citazione:||Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Lunetta, C., Traynor, B., et al. (2016). ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion. NEUROBIOLOGY OF AGING, 39, 218-218.e8 [10.1016/j.neurobiolaging.2015.11.027].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion|
|Autori:||Chiò, A; Mora, G; Sabatelli, M; Caponnetto, C; Lunetta, C; Traynor, B; Johnson, J; Nalls, M; Calvo, A; Moglia, C; Borghero, G; Trojsi, F; La Bella, V; Volanti, P; Simone, I; Salvi, F; Logullo, F; Riva, N; Carrera, P; Giannini, F; Mandrioli, J; Tanel, R; Capasso, M; Tremolizzo, L; Battistini, S; Murru, M; Origone, P; Zollino, M; Penco, S; Mazzini, L; D'Alfonso, S; Restagno, G; Brunetti, M; Barberis, M; Conforti, F; Logroscino, G; Bartolomei, I; Mancardi, G; Mandich, P; Marinou, K; Sideri, R; Mosca, L; Lauria Pinter, G; Corbo, M; Fini, N; Fasano, A; Arosio, A; Ferrarese, C; Tedeschi, G; Monsurrò, M; Piccirillo, G; Femiano, C; Bersano, A; Corrado, L; Bagarotti, A; Spataro, R; Colletti, T; Conte, A; Luigetti, M; Lattante, S; Marangi, G; Santarelli, M; Petrucci, A; Ricci, C; Benigni, M; Casale, F; Marrali, G; Fuda, G; Ossola, I; Cammarosano, S; Ilardi, A; Manera, U; Bertuzzo, D; Tanel, R; Pisano, F; Costantino, E; Pani, C; Puddu, R; Caredda, C; Piras, V; Tranquilli, S; Cuccu, S; Corongiu, D; Melis, M; Milia, A; Marrosu, F; Marrosu, M; Floris, G; Cannas, A; Cuccu, S; Tranquilli, S; Ticca, A; Pugliatti, M; Pirisi, A; Parish, L; Occhineri, P; Ortu, E; Cau, T; Loi, D|
|Data di pubblicazione:||2016|
|Rivista:||NEUROBIOLOGY OF AGING|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neurobiolaging.2015.11.027|
|Appare nelle tipologie:||01 - Articolo su rivista|