ε-Sarcoglycan: Unraveling the Myoclonus-Dystonia Gene

Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding epsilon-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD. To date, the exact role of epsilon-sarcoglycan and the pathogenic mechanisms that lead to MD are still unknown. However, there are more than 40 reported isoforms of human epsilon-sarcoglycan, pointing to a complex biology of this protein. Additionally, some of these are brain-specific isoforms, which may suggest an important role within the central nervous system. In the present review, we aim to provide an overview of the current state of knowledge of epsilon-sarcoglycan. We will focus on the genetic landscape of SGCE and the presence and plausible role of epsilon-sarcoglycan in the brain. Finally, we discuss the importance of the brain-specific isoforms and hypothesize that SGCE may play essential roles in normal synaptic functioning and their alteration will be strongly related to MD.