SGCE isoform characterization and expression in human brain: implications for myoclonus-dystonia pathogenesis?

Myoclonus-dystonia (M-D) is a neurological movement disorder with involuntary jerky and dystonic movements as major symptoms. About 50% of M-D patients have a mutation in e-sarcoglycan (SGCE), a maternally imprinted gene that is widely expressed. As little is known about SGCE function, one can only speculate about the pathomechanisms of the exclusively neurological phenotype in M-D. We characterized different SGCE isoforms in the human brain using ultra-deep sequencing. We show that a major brain-specific isoform is differentially expressed in the human brain with a notably high expression in the cerebellum, namely in the Purkinje cells and neurons of the dentate nucleus. Its expression was low in the globus pallidus and moderate to low in caudate nucleus, putamen and substantia nigra. Our data are compatible with a model in which dysfunction of the cerebellum is involved in the pathogenesis of M-D. European Journal of Human Genetics (2011) 19, 438-444; doi:10.1038/ejhg.2010.206; published online 15 December 2010