title: Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion.
abstract: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are the main syndromes of the chromosome 9 ORF72 (C9ORF72) hexanucleotide repeat expansion, but studies have shown a substantial phenotypic diversity that includes psychiatric presentations. This study describes hippocampal sclerosis dementia (HSD) in carriers of the C9ORF72 mutation. We compared clinical and neuropathological features of HSD in carriers and noncarriers autopsied at Johns Hopkins. Carriers presented with amnesia, agitation, dissocial behavior, and impaired self-care, whereas noncarriers showed little agitation. The groups were not dissimilar in cognitive or motor dysfunction. Neuropathological examination of carriers showed cerebellar neuronal inclusions positive for ubiquitin, p62, and ubiquilin-2, and negative for TAR DNA-binding protein 43. Noncarriers did not have cerebellar inclusions. C9ORF72 repeat-associated non-ATG translation was confirmed by immunohistochemistry. These observations broaden the C9ORF72 phenotype and place HSD in the FTD spectrum. The amnesic phenotype of HSD, which is consistent with the focal hippocampal atrophy, should be included in clinical categorizations of FTD.
authors.affiliation: Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Sloane
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Renton
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Brain Sciences Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.affiliation: Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Crain
authors.affiliation: Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainsville, FL, USA; Genetics Institute, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Reid
authors.affiliation: Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainsville, FL, USA; Genetics Institute, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zu
authors.affiliation: Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainsville, FL, USA; Genetics Institute, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Laura P W
authors.initials: LP
authors.lastname: Ranum
authors.affiliation: Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Rabins
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA. Electronic address: conyike1@johnshopkins.edu.
authors.forename: Chiadi U
authors.initials: CU
authors.lastname: Onyike
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology*; D056726:Genetic Association Studies; D006579:Heterozygote; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D012598:Sclerosis
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: C9ORF72 hexanucleotide repeat expansion; Dementia; Frontotemporal dementia; Hippocampal sclerosis