Title: Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2
Authors: Van Damme, Philip ×
Veldink, J H
van Blitterswijk, M
Corveleyn, A
van Vught, P W J
Thijs, Vincent
Dubois, Bénédicte
Matthijs, Gert
van den Berg, L H
Robberecht, Wim #
Issue Date: Jun-2011
Publisher: Advanstar Communications
Series Title: Neurology vol:76 issue:24 pages:2066-2072
Abstract: OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons that results in progressive muscle weakness and limits survival to 2-5 years after disease onset. Intermediate CAG repeat expansions in ataxin 2 (ATXN2), the causative gene of spinocerebellar ataxia type 2 (SCA2), have been implicated in sporadic ALS. We studied ATXN2 in a large cohort of patients with sporadic and familial ALS. METHODS: We determined ATXN2 CAG repeat size in 1,948 sporadic and familial ALS cases and 2,002 controls from Belgium and the Netherlands. RESULTS: In controls, the maximal ATXN2 repeat size was 31. In sporadic ALS, a significant amount of longer repeat sizes (≥32, range 32-39) were encountered (in 0.5% or 10/1,845 ALS cases, vs 0% in controls, p = 0.0006). Receiver operating characteristic analysis showed that a cutoff of ≥29 appeared optimal to discriminate ALS from control (p = 0.036, odds ratio [OR] 1.92, 95% confidence interval [CI] 1.04-3.64). A meta-analysis with the previously published results from the United States showed that the association between a repeat length of ≥29 and ALS became stronger (p < 0.0001, OR 2.93, 95% CI 1.73-4.98). In unexplained familial ALS, we found an intermediate repeat expansion of 31 and a homozygous repeat expansion of 33 each in 1.1% of families. The phenotype of patients with ALS with expanded repeat sizes ranged from rapidly progressive typical ALS to slowly progressive ALS with reduced sensory nerve action potentials. CONCLUSION: Our data reveal a novel genetic overlap between ALS and SCA2.
ISSN: 0028-3878
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Department of Human Genetics - miscellaneous
Laboratory for Neurobiology
Laboratory for Neuroimmunology
× corresponding author
# (joint) last author

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