Gene expression of iPSC-derived neurons from patient with Mohr-Tranebjaerg syndrome and healthy control

Mohr-Tranebjaerg syndrome (MTS) is a neurodegenerative disease caused by mutations in Translocase of Inner Mitochondrial Membrane 8A/Deafness Dystonia Protein 1 (TIMM8A/DDP1), which encodes TIMM8a/DDP1 located in the intermembrane space (IMS) of mitochondria. Up to now, the pathophysiology of MTS remains unclear. In this study, we established induced pluripotent stem cells (iPSCs) derived from MTS patient carrying the TIMM8a loss-of-function pathogenic variant, p.Q75fs95* to study the mechanism of MTS. We found that MTS-iPSCs presented defects in neuronal differentiation, exhibited smaller somata, fewer branches and shorter neurites, accompanied by mitochondrial dysfunction including fragmented mitochondria, reduced ATP and elevated ROS. Overall design: To understand the molecular mechanism of TIMM8a mutaion on neuronal differentiation, we compared the gene expression of iPSC-derived neurons from a MTS patient and a healthy control.