Investigating the molecular and cellular basis of ε-sarcoglycan-associated myoclonus-dystonia in an iPSC-derived neuronal model

SGCE-related myoclonus-dystonia (M-D) underlies the epigenetic process of imprinting. This leads to the phenomenon of reduced penetrance upon maternal transmission of a pathogenic variant. Our previous work revealed that induced pluripotent stem cell (iPSC)-derived cortical neurons of carriers of pathogenic SGCE variants have been shown to serve as an adequate disease model for SGCE-related M-D, enabling the investigation of functional properties, such as the cellular localization of ε-sarcoglycan. Interestingly, ε-sarcoglycan has been linked to the dystrophin-associated glycoprotein complex (DGC) which is located at the plasma membrane and varies in its composition. Here, we investigate the molecular and cellular basis of
epsilon-sarcoglycan-related myoclonus-dystonia in an iPSC-derived neuronal model from patients with pathogenic variants in SGCE.