Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia

Cinzia Gellera, Cinzia Tiloca, Roberto Del Bo, Lucia Corrado, Viviana Pensato, Jennifer Agostini, Cristina Cereda, Antonia Ratti, Barbara Castellotti, Stefania Corti, Alessandra Bagarotti, Annachiara Cagnin, Pamela Milani, Carlo Gabelli, Giulietta Riboldi, Letizia Mazzini, Gianni Sorarù, Sandra D'Alfonso, Franco Taroni, Giacomo Pietro Comi & 2 others Nicola Ticozzi, Vincenzo Silani

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Abstract

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD. Methods: We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only. Results: We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant. Conclusions: Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.

Original languageEnglish
Pages (from-to)183-187
Number of pages5
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume84
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Mutation
Genes
Motor Neurons
Blood Donors
Proline
Neurodegenerative Diseases
Gene

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

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Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia. / Gellera, Cinzia; Tiloca, Cinzia; Del Bo, Roberto; Corrado, Lucia; Pensato, Viviana; Agostini, Jennifer; Cereda, Cristina; Ratti, Antonia; Castellotti, Barbara; Corti, Stefania; Bagarotti, Alessandra; Cagnin, Annachiara; Milani, Pamela; Gabelli, Carlo; Riboldi, Giulietta; Mazzini, Letizia; Sorarù, Gianni; D'Alfonso, Sandra; Taroni, Franco; Comi, Giacomo Pietro; Ticozzi, Nicola; Silani, Vincenzo.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 84, No. 2, 02.2013, p. 183-187.

Research output: Contribution to journalArticle

Gellera, Cinzia ; Tiloca, Cinzia ; Del Bo, Roberto ; Corrado, Lucia ; Pensato, Viviana ; Agostini, Jennifer ; Cereda, Cristina ; Ratti, Antonia ; Castellotti, Barbara ; Corti, Stefania ; Bagarotti, Alessandra ; Cagnin, Annachiara ; Milani, Pamela ; Gabelli, Carlo ; Riboldi, Giulietta ; Mazzini, Letizia ; Sorarù, Gianni ; D'Alfonso, Sandra ; Taroni, Franco ; Comi, Giacomo Pietro ; Ticozzi, Nicola ; Silani, Vincenzo. / Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia. In: Journal of Neurology, Neurosurgery and Psychiatry. 2013 ; Vol. 84, No. 2. pp. 183-187.
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abstract = "Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90{\%} penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD. Methods: We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only. Results: We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant. Conclusions: Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.",
author = "Cinzia Gellera and Cinzia Tiloca and {Del Bo}, Roberto and Lucia Corrado and Viviana Pensato and Jennifer Agostini and Cristina Cereda and Antonia Ratti and Barbara Castellotti and Stefania Corti and Alessandra Bagarotti and Annachiara Cagnin and Pamela Milani and Carlo Gabelli and Giulietta Riboldi and Letizia Mazzini and Gianni Sorar{\`u} and Sandra D'Alfonso and Franco Taroni and Comi, {Giacomo Pietro} and Nicola Ticozzi and Vincenzo Silani",
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T1 - Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia

AU - Gellera, Cinzia

AU - Tiloca, Cinzia

AU - Del Bo, Roberto

AU - Corrado, Lucia

AU - Pensato, Viviana

AU - Agostini, Jennifer

AU - Cereda, Cristina

AU - Ratti, Antonia

AU - Castellotti, Barbara

AU - Corti, Stefania

AU - Bagarotti, Alessandra

AU - Cagnin, Annachiara

AU - Milani, Pamela

AU - Gabelli, Carlo

AU - Riboldi, Giulietta

AU - Mazzini, Letizia

AU - Sorarù, Gianni

AU - D'Alfonso, Sandra

AU - Taroni, Franco

AU - Comi, Giacomo Pietro

AU - Ticozzi, Nicola

AU - Silani, Vincenzo

PY - 2013/2

Y1 - 2013/2

N2 - Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD. Methods: We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only. Results: We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant. Conclusions: Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.

AB - Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD. Methods: We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only. Results: We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant. Conclusions: Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.

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