Frontotemporal dementia due toC9ORF72mutations
Year: 2012
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion. METHODS: A total of 648 patients with frontotemporal dementia (FTD)-related clinical diagnoses and Alzheimer disease (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats (C9+). Clinical and neuroimaging data were compared between C9+ (15 behavioral variant FTD [bvFTD], 11 FTD-motor neuron disease [MND], 5 amyotrophic lateral sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS). RESULTS: All C9+ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first evaluation, C9+ bvFTD patients had more delusions and greater impairment of working memory, but milder eating dysregulation compared to bvFTD noncarriers. C9+FTD-MND patients had a trend for longer survival and had an earlier age at onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more thalamic atrophy in FTD and FTD-MND carriers than in noncarriers. CONCLUSIONS: Patients with the C9ORF72 hexanucleotide repeat expansion develop bvFTD, ALS, or FTD-MND with similar clinical and imaging features to sporadic cases. Other FTD spectrum diagnoses and AD dementia appear rare or absent among C9+ individuals. Longer survival in C9+ FTD-MND suggests slower disease progression and thalamic atrophy represents a novel and unexpected feature.
Source: Neurology
Authors: Sharon J. Sha, Leonel T. Takada, Katherine P. Rankin, Jennifer S. Yokoyama, Nicola J. Rutherford, Jamie C. Fong, Baber Khan, Anna Karydas, Matt C. Baker, Mariely DeJesus-Hernandez, Mochtar Pribadi, Giovanni Coppola, Daniel H. Geschwind, Rosa Rademakers, Suzee E. Lee, William Seeley, Bruce L. Miller, Adam L. Boxer
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Genetic, Genomic, and Imaging Biomarkers in Degenerative Dementia, Investigating the role of bvFTD-affected networks in socioemotional behavior, Frontotemporal Dementias: Genotypes and Phenotypes, Progranulin: Mutation and Regulation in Neurodegenerative disease, Detecting presymptomatic disease in inherited frontotemporal dementia, G682375611, Eye Movement Control in Normal Elderly and MCI, Progranulin, TDP-43 and Cell Death, Novel Genetic Risk Factors for Alzheimer's Disease (AD) & Frontotemporal Dementia, The Four Repeat Tauopathy Neuroimaging Initiative, Frontotemporal Dementia: Genes, Images, and Emotions, New Approaches to Dementia Heterogeneity
OpenAlex ID: W2043533588