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Expanding the spectrum of C9ORF72-related neurodegenerative disorders in the Greek population

  • Chrisoula Kartanou
    Correspondence
    Corresponding author at: Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, 74 Vas. Sophias Ave., 11528 Athens, Greece.
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Zoi Kontogeorgiou
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Michail Rentzos
    Affiliations
    1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Constantin Potagas
    Affiliations
    Neuropsychology and Speech Pathology Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Stavroula Aristeidou
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Elisabeth Kapaki
    Affiliations
    Unit of Neurochemistry and Biological Markers, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • George P. Paraskevas
    Affiliations
    Unit of Neurochemistry and Biological Markers, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Vasilios C. Constantinides
    Affiliations
    Unit of Neurochemistry and Biological Markers, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Leonidas Stefanis
    Affiliations
    1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece
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  • Sokratis G. Papageorgiou
    Affiliations
    1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Henry Houlden
    Affiliations
    MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
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  • Marios Panas
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Author Footnotes
    1 Equal contribution.
    Georgios Koutsis
    Footnotes
    1 Equal contribution.
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Author Footnotes
    1 Equal contribution.
    Georgia Karadima
    Footnotes
    1 Equal contribution.
    Affiliations
    Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
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  • Author Footnotes
    1 Equal contribution.
Published:October 05, 2022DOI:https://doi.org/10.1016/j.jns.2022.120450

      Highlights

      • The frequency of the C9ORF72 repeat expansion in Greek patients with neurodegenerative disorders remains among the highest in Europe
      • The C9ORF72 expansion does not seem to be a common cause of PD in Greece
      • No C9ORF72 repeat expansions detected in a Greek HSP and control cohort
      • Our study highlights the importance of implementing C9ORF72 genetic test in routine laboratory testing

      Abstract

      The C9ORF72 hexanucleotide repeat expansion is an established cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and has also been associated with Huntington disease (HD)-like syndromes and rarely with Parkinson's disease (PD) and Alzheimer's disease (AD). In the present study we aimed to investigate the genotypic and phenotypic profile of C9ORF72-related disorders in Greece. For this reason, 957 patients (467 with ALS, 53 with HD-like syndromes, 247 with dementia, 175 with PD and 15 with hereditary spastic paraplegia, HSP) and 321 controls were tested for the C9ORF72 repeat expansion. Forty-nine patients with ALS (10.5%), 2 with HD-like syndromes (3.8%), 13 with FTD (11.5%), 1 with AD (1.6%), and 2 with PD (1.1%) were expansion-positive. The expansion was not detected in the HSP or control groups. The results of this study provide an update on the spectrum of C9ORF72-related neurodegenerative diseases, emphasizing the importance of C9ORF72 genetic testing in Greek patients with familial and sporadic ALS and/or FTD and HD-like syndromes.

      Keywords

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