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. 2012 Mar 13;78(11):776-80.
doi: 10.1212/WNL.0b013e318249f697. Epub 2012 Feb 8.

SMN1 gene duplications are associated with sporadic ALS

H M Blauw  1 , C P Barnes, P W J van Vught, W van Rheenen, M Verheul, E Cuppen, J H Veldink, L H van den Berg
Affiliations

SMN1 gene duplications are associated with sporadic ALS

H M Blauw et al. Neurology. .

Abstract

Objective: To investigate the role of SMN1 and SMN2 copy number variation and point mutations in amyotrophic lateral sclerosis (ALS) pathogenesis in a large population.

Methods: We conducted a genetic association study including 847 patients with ALS and 984 controls. We used multiplexed ligation-dependent probe amplification (MLPA) assays to determine SMN1 and SMN2 copy numbers and examined effects on disease susceptibility and disease course. Furthermore, we sequenced SMN genes to determine if SMN mutations were more prevalent in patients with ALS. A meta-analysis was performed with results from previous studies.

Results: SMN1 duplications were associated with ALS susceptibility (odds ratio [OR] 2.07, 95% confidence interval [CI] 1.34-3.20, p = 0.001). A meta-analysis with previous data including 3,469 individuals showed a similar effect: OR 1.85, 95% CI 1.18-2.90, p = 0.008). SMN1 deletions and SMN2 copy number status were not associated with ALS. SMN1 or SMN2 copy number variants had no effect on survival or the age at onset of the disease. We found no enrichment of SMN point mutations in patients with ALS.

Conclusions: Our data provide firm evidence for a role of common SMN1 duplications in ALS, and raise new questions regarding the disease mechanisms involved.

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Figures

Figure
Figure. Combined analysis of SMN1 duplications
The table shows per study the frequency and absolute numbers and risk estimate of SMN1 duplications. ALS = amyotrophic lateral sclerosis; CI = confidence interval; OR = odds ratio; p = logistic.
See this image and copyright information in PMC

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