Gene expression profiling in SMA I and III patients

ABSTRACT: Proximal spinal muscular atrophy (SMA) is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and characterized by progressive paralysis caused by degeneration of α–motor neurons of the spinal cord. To better understand the effects of SMN gene defect in SMA skeletal muscle tissues we performed a transcriptional analysis of muscle specimens of patient affected by the two extreme forms of SMA: the most severe type I and the mild type III. Patients of both groups had a variable SMN2 copy number that did not correlate with phenotype severity. The two forms of SMA resulted with a distinct expression profile: in SMA III patients the reduced number of modified genes suggests a proximity to normal condition, whereas in SMA I patients there is highly deregulated picture of gene expression. Genes implicated in signal transduction were up regulated in SMA III condition whereas those typical of energy metabolism and muscle contraction were consistently down regulated in severe disease type. Microarray results were validated, and the expression pattern of gene networks involved in atrophy signaling were completed by RQ-PCR. The analysis shows that specific atrophy pathways are involved: IGF/PI3K/Akt and those regulating MNK1-2 (more precisely TNF-α/p38 MAPK and Ras/ERK pathways). The results suggest also a different picture of atrophy pathways in the two forms of SMA. In particular in SMA I muscles, p38 may be the protein synthesis regulator. Moreover SMA III profile appear to be the result of a more complex transcriptome given by the concurrent presence of atrophic and hyperthrophic fibers. This more favorable condition might be due to action of MTOR whose over expression in SMA III could lead to a compensative hypertrophy. Keywords: disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE8359 | GEO | 2009/06/08

SECONDARY ACCESSION(S): PRJNA101379

REPOSITORIES: GEO