Faithful SGCE imprinting in iPSC-derived cortical neurons: An endogenous cellular model of myoclonus-dystonia

Karen Grütz, Philip Seibler, Anne Weissbach, Katja Lohmann, Francesca A. Carlisle, Derek J. Blake, Ana Westenberger, Christine Klein*, Anne Grünewald

*Corresponding author for this work
1 Citation (Scopus)


In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been challenged. We generated iPSC-derived cortical neurons from myoclonus-dystonia patients with mutations (W100G and R102X) in the maternally imprinted ϵ-sarcoglycan (SGCE) gene and analysed properties such as imprinting, mRNA and protein expression. Comparison of the promoter during reprogramming and differentiation showed tissue-independent differential methylation. DNA sequencing with methylation-specific primers and cDNA analysis in patient neurons indicated selective expression of the mutated paternal SGCE allele. While fibroblasts only expressed the ubiquitous mRNA isoform, brain-specific SGCE mRNA and ϵ-sarcoglycan protein were detected in iPSC-derived control neurons. However, neuronal protein levels were reduced in both mutants. Our phenotypic characterization highlights the suitability of iPSC-derived cortical neurons with SGCE mutations for myoclonus-dystonia research and, in more general terms, prompts the use of iPSC-derived cellular models to study epigenetic mechanisms impacting on health and disease.

Original languageEnglish
Article number41156
JournalScientific Reports
Publication statusPublished - 03.02.2017


Dive into the research topics of 'Faithful SGCE imprinting in iPSC-derived cortical neurons: An endogenous cellular model of myoclonus-dystonia'. Together they form a unique fingerprint.

Cite this