C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population

Antonino Cannas, Paolo Solla, Giuseppe Borghero, Gian Luca Floris, Adriano Chio, Marcello Mario Mascia, Nicola Modugno, Antonella Muroni, Gianni Orofino, Francesca Di Stefano, Andrea Calvo, Cristina Moglia, Gabriella Restagno, Mario Meloni, Rita Farris, Daniela Ciaccio, Roberta Puddu, Melisa Iris Vacca, Rosanna Melis, Maria Rita MurruStefania Tranquilli, Daniela Corongiu, Marcella Rolesu, Stefania Cuccu, Maria Giovanna Marrosu, Francesco Marrosu

Research output: Contribution to journalArticle

Abstract

The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson’s disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20–30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.

Original languageEnglish
JournalJournal of Neurology
DOIs
Publication statusAccepted/In press - Aug 15 2015

Fingerprint

Parkinsonian Disorders
Psychotic Disorders
Parkinson Disease
Dementia
Population
Frontotemporal Dementia
Genes
Progressive Supranuclear Palsy
Multiple System Atrophy
Lewy Body Disease
Amyotrophic Lateral Sclerosis
Levodopa
Virulence

Keywords

  • Atypical parkinsonian syndromes
  • C9ORF72 short expansion
  • Parkinson’s disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population. / Cannas, Antonino; Solla, Paolo; Borghero, Giuseppe; Floris, Gian Luca; Chio, Adriano; Mascia, Marcello Mario; Modugno, Nicola; Muroni, Antonella; Orofino, Gianni; Di Stefano, Francesca; Calvo, Andrea; Moglia, Cristina; Restagno, Gabriella; Meloni, Mario; Farris, Rita; Ciaccio, Daniela; Puddu, Roberta; Vacca, Melisa Iris; Melis, Rosanna; Murru, Maria Rita; Tranquilli, Stefania; Corongiu, Daniela; Rolesu, Marcella; Cuccu, Stefania; Marrosu, Maria Giovanna; Marrosu, Francesco.

In: Journal of Neurology, 15.08.2015.

Research output: Contribution to journalArticle

Cannas, A, Solla, P, Borghero, G, Floris, GL, Chio, A, Mascia, MM, Modugno, N, Muroni, A, Orofino, G, Di Stefano, F, Calvo, A, Moglia, C, Restagno, G, Meloni, M, Farris, R, Ciaccio, D, Puddu, R, Vacca, MI, Melis, R, Murru, MR, Tranquilli, S, Corongiu, D, Rolesu, M, Cuccu, S, Marrosu, MG & Marrosu, F 2015, 'C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population', Journal of Neurology. https://doi.org/10.1007/s00415-015-7873-6
Cannas, Antonino ; Solla, Paolo ; Borghero, Giuseppe ; Floris, Gian Luca ; Chio, Adriano ; Mascia, Marcello Mario ; Modugno, Nicola ; Muroni, Antonella ; Orofino, Gianni ; Di Stefano, Francesca ; Calvo, Andrea ; Moglia, Cristina ; Restagno, Gabriella ; Meloni, Mario ; Farris, Rita ; Ciaccio, Daniela ; Puddu, Roberta ; Vacca, Melisa Iris ; Melis, Rosanna ; Murru, Maria Rita ; Tranquilli, Stefania ; Corongiu, Daniela ; Rolesu, Marcella ; Cuccu, Stefania ; Marrosu, Maria Giovanna ; Marrosu, Francesco. / C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population. In: Journal of Neurology. 2015.
@article{8154ceae95a047bfb2e6002f82c70e47,
title = "C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population",
abstract = "The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson’s disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20–30 repeat expansions were detected in four female patients (4.3 {\%}). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.",
keywords = "Atypical parkinsonian syndromes, C9ORF72 short expansion, Parkinson’s disease",
author = "Antonino Cannas and Paolo Solla and Giuseppe Borghero and Floris, {Gian Luca} and Adriano Chio and Mascia, {Marcello Mario} and Nicola Modugno and Antonella Muroni and Gianni Orofino and {Di Stefano}, Francesca and Andrea Calvo and Cristina Moglia and Gabriella Restagno and Mario Meloni and Rita Farris and Daniela Ciaccio and Roberta Puddu and Vacca, {Melisa Iris} and Rosanna Melis and Murru, {Maria Rita} and Stefania Tranquilli and Daniela Corongiu and Marcella Rolesu and Stefania Cuccu and Marrosu, {Maria Giovanna} and Francesco Marrosu",
year = "2015",
month = "8",
day = "15",
doi = "10.1007/s00415-015-7873-6",
language = "English",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",

}

TY - JOUR

T1 - C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population

AU - Cannas, Antonino

AU - Solla, Paolo

AU - Borghero, Giuseppe

AU - Floris, Gian Luca

AU - Chio, Adriano

AU - Mascia, Marcello Mario

AU - Modugno, Nicola

AU - Muroni, Antonella

AU - Orofino, Gianni

AU - Di Stefano, Francesca

AU - Calvo, Andrea

AU - Moglia, Cristina

AU - Restagno, Gabriella

AU - Meloni, Mario

AU - Farris, Rita

AU - Ciaccio, Daniela

AU - Puddu, Roberta

AU - Vacca, Melisa Iris

AU - Melis, Rosanna

AU - Murru, Maria Rita

AU - Tranquilli, Stefania

AU - Corongiu, Daniela

AU - Rolesu, Marcella

AU - Cuccu, Stefania

AU - Marrosu, Maria Giovanna

AU - Marrosu, Francesco

PY - 2015/8/15

Y1 - 2015/8/15

N2 - The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson’s disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20–30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.

AB - The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson’s disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20–30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.

KW - Atypical parkinsonian syndromes

KW - C9ORF72 short expansion

KW - Parkinson’s disease

UR - http://www.scopus.com/inward/record.url?scp=84939249845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939249845&partnerID=8YFLogxK

U2 - 10.1007/s00415-015-7873-6

DO - 10.1007/s00415-015-7873-6

M3 - Article

C2 - 26275564

AN - SCOPUS:84939249845

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

ER -