Journal of Neurology

, Volume 262, Issue 11, pp 2498–2503 | Cite as

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 Murru
  • Stefania Tranquilli
  • Daniela Corongiu
  • Marcella Rolesu
  • Stefania Cuccu
  • Maria Giovanna Marrosu
  • Francesco Marrosu
Original Communication
First Online:
Received:
Revised:
Accepted:

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

Parkinson’s disease Atypical parkinsonian syndromes C9ORF72 short expansion 
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Notes

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards statement

This study has been approved by the appropriate institutional authority and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Supplementary material

415_2015_7873_MOESM1_ESM.doc (44 kb)
Supplementary material 1 (DOC 44 kb)
415_2015_7873_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (DOCX 18 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Antonino Cannas
    • 1
  • Paolo Solla
    • 1
  • Giuseppe Borghero
    • 1
  • Gian Luca Floris
    • 1
  • Adriano Chio
    • 2
  • Marcello Mario Mascia
    • 1
  • Nicola Modugno
    • 3
  • Antonella Muroni
    • 1
  • Gianni Orofino
    • 1
  • Francesca Di Stefano
    • 1
  • Andrea Calvo
    • 2
  • Cristina Moglia
    • 2
  • Gabriella Restagno
    • 2
  • Mario Meloni
    • 1
  • Rita Farris
    • 1
  • Daniela Ciaccio
    • 1
  • Roberta Puddu
    • 1
  • Melisa Iris Vacca
    • 1
  • Rosanna Melis
    • 1
  • Maria Rita Murru
    • 4
  • Stefania Tranquilli
    • 4
  • Daniela Corongiu
    • 4
  • Marcella Rolesu
    • 4
  • Stefania Cuccu
    • 4
  • Maria Giovanna Marrosu
    • 4
  • Francesco Marrosu
    • 1
  1. 1.Department of Neurology, Movement Disorders CenterPoliclinico Universitario Monserrato, University of CagliariMonserratoItaly
  2. 2.Dipartimento di Neuroscienze ‘Rita Levi Montalcini’, Centro Regionale Esperto per la SLA (CRESLA)Università di TorinoTurinItaly
  3. 3.I.R.C.C.S. NeuromedPozzilliItaly
  4. 4.Laboratorio Centro Sclerosi Multipla, Ospedale BinaghiUniversità di CagliariMonserratoItaly

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