Journal article
Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition
J Hauke, M Riessland, S Lunke, IY Eyüpoglu, I Blümcke, A El-osta, B Wirth, E Hahnen
Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2009
DOI: 10.1093/hmg/ddn357
Abstract
Spinal muscular atrophy (SMA), a common neuromuscular disorder, is caused by homozygous absence of the survival motor neuron gene 1 (SMN1), while the disease severity is mainly influenced by the number of SMN2 gene copies. This correlation is not absolute, suggesting the existence of yet unknown factors modulating disease progression. We demonstrate that the SMN2 gene is subject to gene silencing by DNA methylation. SMN2 contains four CpG islands which present highly conserved methylation patterns and little interindividual variations in SMN1-deleted SMA patients. The comprehensive analysis of SMN2 methylation in patients suffering from severe versus mild SMA carrying identical SMN2 copy num..
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Funding Acknowledgements
This work was kindly supported by the 'Initiative Forschung und Therapie fur SMA' (to E. H. and to B. W.), the 'Koln Fortune Program/Faculty of Medicine, University of Cologne' (to E. H.), the 'Deutsche Forschungsgemeinschaft (DFG)' (to E. H., to I. B. and to B. W.), the 'Wilhelm Sander Foundation' (to E. H., I.Y.E. and I. B.), the 'Families of Spinal Muscular Atrophy' (to B. W. and E. H.) and the 'Center for Molecular Medicine Cologne' (to B. W. and E. H.). The 'Monash International Post graduate Research Scholarship (MIPRS)' and the 'Monash Graduate Scholarship (MGS)' (to S. L.). Funding to pay the Open Access charge was provided by the 'Initiative Forschung und Therapie fur SMA'.