caa a22 4500 445860979 CHVBK 20180317145442.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00439-011-1000-2 doi (NATIONALLICENCE)springer-10.1007/s00439-011-1000-2 ATXN - 2 CAG repeat expansions are interrupted in ALS patients [Elektronische Daten] [Lucia Corrado, Letizia Mazzini, Gaia Oggioni, Bernadetta Luciano, Michela Godi, Alfredo Brusco, Sandra D'Alfonso] It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing >30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p=0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded (>32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles. Springer-Verlag, 2011 Corrado Lucia Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut Mazzini Letizia Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy aut Oggioni Gaia Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy aut Luciano Bernadetta Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut Godi Michela Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut Brusco Alfredo Department of Genetics Biology and Biochemistry, Università degli Studi di Torino, Torino, Italy aut D'Alfonso Sandra Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut Human Genetics Springer-Verlag 130/4(2011-10-01), 575-580 0340-6717 130:4<575 2011 130 439 https://doi.org/10.1007/s00439-011-1000-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-1000-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Corrado Lucia Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Mazzini Letizia Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy aut NATIONALLICENCE 700 1- Oggioni Gaia Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy aut NATIONALLICENCE 700 1- Luciano Bernadetta Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Godi Michela Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut NATIONALLICENCE 700 1- Brusco Alfredo Department of Genetics Biology and Biochemistry, Università degli Studi di Torino, Torino, Italy aut NATIONALLICENCE 700 1- D'Alfonso Sandra Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100, Novara, Italy aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/4(2011-10-01), 575-580 0340-6717 130:4<575 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer