1. Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype
- Author
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Rutherford, Nicola J, Heckman, Michael G, DeJesus-Hernandez, Mariely, Baker, Matt C, Soto-Ortolaza, Alexandra I, Rayaprolu, Sruti, Stewart, Heather, Finger, Elizabeth, Volkening, Kathryn, Seeley, William W, Hatanpaa, Kimmo J, Lomen-Hoerth, Catherine, Kertesz, Andrew, Bigio, Eileen H, Lippa, Carol, Knopman, David S, Kretzschmar, Hans A, Neumann, Manuela, Caselli, Richard J, White, Charles L, Mackenzie, Ian R, Petersen, Ronald C, Strong, Michael J, Miller, Bruce L, Boeve, Bradley F, Uitti, Ryan J, Boylan, Kevin B, Wszolek, Zbigniew K, Graff-Radford, Neill R, Dickson, Dennis W, Ross, Owen A, and Rademakers, Rosa
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Alzheimer's Disease Related Dementias (ADRD) ,Acquired Cognitive Impairment ,ALS ,Frontotemporal Dementia (FTD) ,Rare Diseases ,Dementia ,Genetics ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aging ,Clinical Research ,Brain Disorders ,2.1 Biological and endogenous factors ,Neurological ,Adult ,Aged ,Aged ,80 and over ,Amyotrophic Lateral Sclerosis ,C9orf72 Protein ,DNA Repeat Expansion ,Female ,Frontotemporal Dementia ,Genetic Predisposition to Disease ,Humans ,Male ,Middle Aged ,Proteins ,Amyotrophic lateral sclerosis ,Frontotemporal dementia ,C9ORF72 ,Repeat-expansion disease ,Association study ,Clinical Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.
- Published
- 2012