Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2

P. Van Damme, J. H. Veldink, M. Van Blitterswijk, A. Corveleyn, P. W.J. Van Vught, V. Thijs, B. Dubois, G. Matthijs, L. H. Van Den Berg, W. Robberecht

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2066-2072
Number of pages7
Issue number24
StatePublished - Jun 14 2011

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2'. Together they form a unique fingerprint.

Cite this