ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Adriano Chiò, Gabriele Mora, Mario Sabatelli, Claudia Caponnetto, Christian Lunetta, Bryan J. Traynor, Janel O. Johnson, Mike A. Nalls, Andrea Calvo, Cristina Moglia, Giuseppe Borghero, Francesca Trojsi, Vincenzo La Bella, Paolo Volanti, Isabella Simone, Fabrizio Salvi, Francesco O. Logullo, Nilo Riva, Paola Carrera, Fabio GianniniJessica Mandrioli, Raffaella Tanel, Margherita Capasso, Lucio Tremolizzo, Stefania Battistini, Maria Rita Murru, Paola Origone, Marcella Zollino, Silvana Penco, Letizia Mazzini, Sandra D'Alfonso, Gabriella Restagno, Maura Brunetti, Marco Barberis, Francesca L. Conforti, Giancarlo Logroscino, Ilaria Bartolomei, Gianluigi Mancardi, Paola Mandich, Kalliopi Marinou, Riccardo Sideri, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Nicola Fini, Antonio Fasano, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Bersano, Lucia Corrado, Alessandra Bagarotti, Rossella Spataro, Tiziana Colletti, Amelia Conte, Marco Luigetti, Serena Lattante, Giuseppe Marangi, Marialuisa Santarelli, Antonio Petrucci, Claudia Ricci, Michele Benigni, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Ilardi, Umberto Manera, Davide Bertuzzo, Raffaella Tanel, Fabrizio Pisano, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Stefania Cuccu, Stefania Tranquilli, Anna Ticca, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Enzo Ortu, Tea B. Cau, Daniela Loi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)218.e5-218.e8
JournalNeurobiology of Aging
Volume39
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Amyotrophic Lateral Sclerosis
Regulator Genes
Alleles
Italy

Keywords

  • Amyotrophic lateral sclerosis
  • ATXN2
  • C9ORF72
  • Phenotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion. / 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; Tanel, Raffaella; 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; Cuccu, Stefania; Tranquilli, Stefania; Ticca, Anna; Pugliatti, Maura; Pirisi, Angelo; Parish, Leslie D.; Occhineri, Patrizia; Ortu, Enzo; Cau, Tea B.; Loi, Daniela.

In: Neurobiology of Aging, Vol. 39, 01.03.2016, p. 218.e5-218.e8.

Research output: Contribution to journalArticle

Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, BJ, Johnson, JO, Nalls, MA, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, FO, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, MR, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, FL, 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, MR, 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, MG, Floris, G, Cannas, A, Cuccu, S, Tranquilli, S, Ticca, A, Pugliatti, M, Pirisi, A, Parish, LD, Occhineri, P, Ortu, E, Cau, TB & Loi, D 2016, 'ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion', Neurobiology of Aging, vol. 39, pp. 218.e5-218.e8. https://doi.org/10.1016/j.neurobiolaging.2015.11.027
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 ; Tanel, Raffaella ; 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 ; Cuccu, Stefania ; Tranquilli, Stefania ; Ticca, Anna ; Pugliatti, Maura ; Pirisi, Angelo ; Parish, Leslie D. ; Occhineri, Patrizia ; Ortu, Enzo ; Cau, Tea B. ; Loi, Daniela. / ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion. In: Neurobiology of Aging. 2016 ; Vol. 39. pp. 218.e5-218.e8.
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abstract = "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.",
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TY - JOUR

T1 - ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

AU - Chiò, Adriano

AU - Mora, Gabriele

AU - Sabatelli, Mario

AU - Caponnetto, Claudia

AU - Lunetta, Christian

AU - Traynor, Bryan J.

AU - Johnson, Janel O.

AU - Nalls, Mike A.

AU - Calvo, Andrea

AU - Moglia, Cristina

AU - Borghero, Giuseppe

AU - Trojsi, Francesca

AU - La Bella, Vincenzo

AU - Volanti, Paolo

AU - Simone, Isabella

AU - Salvi, Fabrizio

AU - Logullo, Francesco O.

AU - Riva, Nilo

AU - Carrera, Paola

AU - Giannini, Fabio

AU - Mandrioli, Jessica

AU - Tanel, Raffaella

AU - Capasso, Margherita

AU - Tremolizzo, Lucio

AU - Battistini, Stefania

AU - Murru, Maria Rita

AU - Origone, Paola

AU - Zollino, Marcella

AU - Penco, Silvana

AU - Mazzini, Letizia

AU - D'Alfonso, Sandra

AU - Restagno, Gabriella

AU - Brunetti, Maura

AU - Barberis, Marco

AU - Conforti, Francesca L.

AU - Logroscino, Giancarlo

AU - Bartolomei, Ilaria

AU - Mancardi, Gianluigi

AU - Mandich, Paola

AU - Marinou, Kalliopi

AU - Sideri, Riccardo

AU - Mosca, Lorena

AU - Lauria Pinter, Giuseppe

AU - Corbo, Massimo

AU - Fini, Nicola

AU - Fasano, Antonio

AU - Arosio, Alessandro

AU - Ferrarese, Carlo

AU - Tedeschi, Gioacchino

AU - Monsurrò, Maria Rosaria

AU - Piccirillo, Giovanni

AU - Femiano, Cinzia

AU - Bersano, Anna

AU - Corrado, Lucia

AU - Bagarotti, Alessandra

AU - Spataro, Rossella

AU - Colletti, Tiziana

AU - Conte, Amelia

AU - Luigetti, Marco

AU - Lattante, Serena

AU - Marangi, Giuseppe

AU - Santarelli, Marialuisa

AU - Petrucci, Antonio

AU - Ricci, Claudia

AU - Benigni, Michele

AU - Casale, Federico

AU - Marrali, Giuseppe

AU - Fuda, Giuseppe

AU - Ossola, Irene

AU - Cammarosano, Stefania

AU - Ilardi, Antonio

AU - Manera, Umberto

AU - Bertuzzo, Davide

AU - Tanel, Raffaella

AU - Pisano, Fabrizio

AU - Costantino, Emanuela

AU - Pani, Carla

AU - Puddu, Roberta

AU - Caredda, Carla

AU - Piras, Valeria

AU - Tranquilli, Stefania

AU - Cuccu, Stefania

AU - Corongiu, Daniela

AU - Melis, Maurizio

AU - Milia, Antonio

AU - Marrosu, Francesco

AU - Marrosu, Maria Giovanna

AU - Floris, Gianluca

AU - Cannas, Antonino

AU - Cuccu, Stefania

AU - Tranquilli, Stefania

AU - Ticca, Anna

AU - Pugliatti, Maura

AU - Pirisi, Angelo

AU - Parish, Leslie D.

AU - Occhineri, Patrizia

AU - Ortu, Enzo

AU - Cau, Tea B.

AU - Loi, Daniela

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - ATXN2

KW - C9ORF72

KW - Phenotype

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U2 - 10.1016/j.neurobiolaging.2015.11.027

DO - 10.1016/j.neurobiolaging.2015.11.027

M3 - Article

VL - 39

SP - 218.e5-218.e8

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -