Spinal muscular atrophy (SMA), caused by a mutation of the SMN gene is an infantile and juvenile neurodegenerative disorder with progressive paralysis caused by the loss of motor neurons. Besides its role in neurons, a deficiency in SMN may have a direct effect on muscle tissue. A research team from Italy, led by Gerolamo Lanfranchi, analyzed muscle biopsies and genomic DNA from peripheral blood of four SMA I and five SMA III patients to investigate which other muscle genes, other than the SMN defect, played a role in atrophy. They used microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe, type I (infantile), and the milder type III (juvenile). The two forms of SMA gave distinct expression signatures. The SMA III muscle transcriptome is close to normal, whereas in SMA I gene expression is significantly altered. Genes implicated in signal transduction were up-regulated in SMA III whereas those involved in energy metabolism and muscle contraction were consistently down-regulated in SMA I. This study indicates that SMA I and III muscles are in different phases: the ‘prolonged’ atrophic condition typical of the SMA I muscle and the coexistence of atrophy and hypertrophy in SMA III muscle. Previous studies have investigated transcriptional changes in mouse or rat muscle atrophied due to physiopathological conditions, but this is the first to use human tissue affected by a genetic atrophic condition.

Références : BMC Med. 2009 Apr 7;7(1):14. [Epub ahead of print]