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Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion
Olga Pletnikova1, Kelly L Sloane2, Alan E Renton3
1Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Neurobiology of Aging
|May 14, 2014
Summary
The chromosome 9 ORF72 (C9ORF72) mutation is linked to hippocampal sclerosis dementia (HSD). This study found HSD in C9ORF72 carriers, expanding the known C9ORF72 disease spectrum.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are primary manifestations of the C9ORF72 gene mutation.
- Phenotypic diversity in C9ORF72-related disorders includes psychiatric symptoms.
Purpose of the Study:
- To describe hippocampal sclerosis dementia (HSD) in individuals with the C9ORF72 mutation.
- To compare clinical and neuropathological features of HSD between C9ORF72 carriers and non-carriers.
Main Methods:
- Comparative analysis of clinical data and post-mortem neuropathological findings.
- Immunohistochemistry to confirm C9ORF72 repeat-associated non-ATG translation and identify protein inclusions.
Main Results:
- C9ORF72 carriers with HSD exhibited amnesia, agitation, dissocial behavior, and impaired self-care.
- Neuropathological examination of carriers revealed specific neuronal inclusions in the cerebellum, absent in non-carriers.
- No significant differences in overall cognitive or motor dysfunction were observed between carriers and non-carriers.
Conclusions:
- Hippocampal sclerosis dementia (HSD) is a newly identified phenotype associated with C9ORF72 mutations.
- These findings broaden the clinical spectrum of C9ORF72 repeat expansion disorders.
- The amnesic presentation of HSD warrants its inclusion in FTD classifications.
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