title: C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population.
abstract: An expanded hexanucleotide repeat in C9ORF72 has been identified as the most common genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia in many populations, including the Greek. Recently, C9ORF72 expansions were reported as the most common genetic cause of Huntington disease (HD) phenocopies in a UK population. In the present study, we screened a selected cohort of 40 Greek patients with HD phenocopies for C9ORF72 hexanucleotide repeat expansions using repeat-primed polymerase chain reaction. We identified 2 patients (5%) with pathologic expansions. The first patient had chorea, behavioral-psychiatric disturbance, cognitive impairment, and a positive family history, fulfilling the strictest criteria for HD phenocopy. The second patient was sporadic and had parkinsonism, behavioral-psychiatric disturbance, and cognitive impairment, corresponding to a broader definition of HD phenocopy. These findings identify C9ORF72 expansions as a frequent cause of HD phenocopies in the Greek population, confirming recent findings in other populations and supporting proposed diagnostic testing for C9ORF72 expansions in patients with HD-like syndromes.
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece. Electronic address: gkoutsi2@otenet.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koutsis
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karadima
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Chrisoula
authors.initials: C
authors.lastname: Kartanou
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Kladi
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Panas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000073885:C9orf72 Protein; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D057180:Frontotemporal Dementia / Q000235:genetics; D006115:Greece; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: C9ORF72; Greek population; Hexanucleotide repeat expansion; Huntington disease; Huntington disease phenocopies; Huntington disease–like syndromes