Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival.

ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry / G. Borghero, M. Pugliatti, F. Marrosu, M.G. Marrosu, M.R. Murru, G. Floris, A. Cannas, L.D. Parish, T.B. Cau, D. Loi, A. Ticca, S. Traccis, U. Manera, A. Canosa, C. Moglia, A. Calvo, M. Barberis, M. Brunetti, A.E. Renton, M.A. Nalls, B.J. Traynor, G. Restagno, A. Chio, F.O. Logullo, I. Simone, G. Logroscino, F. Salvi, I. Bartolomei, M. Capasso, C. Caponnetto, G. Mancardi, P. Mandich, P. Origone, F.L. Conforti, G. Mora, K. Marinou, R. Sideri, C. Lunetta, S. Penco, L. Mosca, R. Nilo, G.L. Pinter, M. Corbo, P. Volanti, J. Mandrioli, N. Fini, E. Georgoulopoulou, L. Tremolizzo, M. Maria Rosaria, G. Tedeschi, V. Cristillo, V. la Bella, R. Spataro, T. Colletti, M. Sabatelli, M. Zollino, A. Conte, M. Luigetti, S. Lattante, G. Marangi, M. Santarelli, A. Petrucci, F. Giannini, S. Battistini, C. Ricci, F. Casale, G. Marrali, G. Fuda, I. Ossola, S. Cammarosano, A. Ilardi, D. Bertuzzo, R. Tanel, F. Pisano, E. Costantino, C. Pani, R. Puddu, C. Caredda, V. Piras, S. Tranquilli, S. Cuccu, D. Corongiu, M. Melis, A. Milia, A. Pirisi, P. Occhineri, E. Ortu. - In: NEUROBIOLOGY OF AGING. - ISSN 1558-1497. - 36:10(2015), pp. 2906.e1-2906.e5. [10.1016/j.neurobiolaging.2015.06.013]

ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Murru M. R.;Loi D.;Manera U.;Sideri R.;Tedeschi G.;Petrucci A.;Piras V.;Melis M.;Ortu E.
2015

Abstract

Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival.
Amyotrophic lateral sclerosis; Ataxin 2 gene; Genetic modifier; Amyotrophic Lateral Sclerosis; Ataxin-2; Female; Humans; Italy; Male; Middle Aged; Risk Factors; Survival Rate; Trinucleotide Repeat Expansion; Genetic Association Studies; Phenotype
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/728337
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