title: ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry.
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.
authors.affiliation: Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Pugliatti
authors.affiliation: Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: Multiple Sclerosis Center Laboratory, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Marrosu
authors.affiliation: Multiple Sclerosis Center Laboratory, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Murru
authors.affiliation: Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Floris
authors.affiliation: Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Cannas
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Parish
authors.affiliation: Azienda Sanitaria Locale n. 2, Olbia-Tempio, Italy.
authors.forename: Tea B
authors.initials: TB
authors.lastname: Cau
authors.affiliation: Azienda Sanitaria Locale n. 2, Olbia-Tempio, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Loi
authors.affiliation: Department of Neurology, Azienda Ospedaliera San Francesco, Nuoro, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ticca
authors.affiliation: Department of Neurology, Ospedale Antonio Segni, Ozieri, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Traccis
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Manera
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, University of Genoa, Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Neurology II, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Barberis
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.affiliation: Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute of Aging, Bethesda, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Renton
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute of Aging, Bethesda, USA.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy; Brain Science Institute, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.affiliation: Laboratory of Molecular Genetics, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Neurology II, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy; Neuroscience Institute of Torino (NIT), Turin, Italy. Electronic address: achio@usa.net.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality; D000067698:Ataxin-2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D015996:Survival Rate; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C000593752:ATXN2 protein, human; D000067698:Ataxin-2
keywords: Amyotrophic lateral sclerosis; Ataxin 2 gene; Genetic modifier