Using a genetic analysis technique known as “next generation sequencing” the scientists identified a defective gene called MEGF10 responsible for the muscle weakness.
The children suffer from severe weakness of the body musculature and of the inner organs like the diaphragm, the main breathing muscle. The consequences are that the little patients are only able to move in a wheelchair and need continuous artificial respiration. These children often have to be tube-fed as well since the musculature of the esophagus does not work properly.
But which role plays the discovered gene here and is involved in muscle growth? In healthy humans the muscle stem cells, so called “satellite cells” stick on muscle fibers and normally remain inactive. If a muscle fiber becomes damaged or muscle growth is stimulated, as it is in muscle training, the satellite cells start to divide, fuse with the muscle fiber and so cause muscle growth. This process is disrupted in the ill children. For them, the necessary protein which is responsible for the attachment of the satellite cells cannot be developed by the mutated MEGF10 gene. Therefore, these cells cannot stick on the muscle fibre – the muscle cannot be repaired any longer.
Prof. Markus Schuelke from the NeuroCure Clinical Research Center of the Cluster of Excellence NeuroCure and the Department of Neuropediatrics of the Charité and Prof. Colin A. Johnson from the Institute of Molecular Medicine of the University Leeds, who jointly directed this research project have emphasized the importance of these new methods for genome analysis and give a positive outlook for the future. “This is good news for families with unexplained rare genetic disorders. These methods enable us to sequence hundreds or even thousands of genes at the same time and discover novel genetic defects even in single patients quickly but also cost effective” explains Markus Schuelke. “Many patients and their families often have been through a diagnostic Odyssey and can now hope that the cause of their disease will be found through this approach.”
*Logan, C.V. et.al.: Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia. Nature Genetics 2011 Nov 20, doi: 10.1038/ng.995.
Prof. Markus Schuelke
NeuroCure Clinical Research Center
Klinik für Pädiatrie mit Schwerpunkt Neurologie
Charité – Universitätsmedizin Berlin
t: +49 30 450 566 468