Modeling DYT1 Dystonia Using Induced Pluripotent Stem Cells.

Published in Annals Of Neurology, 2018

Recommended citation: AR Dinasarapu, DJ Sutcliffe, ME Zwick, HA Jinnah. (2018). "Modeling DYT1 Dystonia Using Induced Pluripotent Stem Cells." Annals Of Neurology, 84, S198-S199.

DYT1 dystonia is an autosomal dominant early‐onset movement disorder characterized by involuntary muscle contraction causing abnormal postures and or movements. It is caused by a 3‐basepair deletion in the TOR1A gene, which encodes torsinA. The mechanisms causing neurological dysfunction remain obscure, but are thought to involve abnormal function of nigral dopamine neurons, striatal interneurons, or even cerebellar Purkinje neurons. Two induced pluripotent stem cell (iPSc) lines were derived from fibroblasts from each of 3 unrelated subjects with DYT1 dystonia and matched controls. All lines were fully characterized for pluripotency markers, morphology, and karyotype. RNA‐Seq was performed and a total of 81 differentially expressed genes between DYT1 and healthy controls with nominal p<0.001 were identified. None of these genes were differentially expressed at a FDR<0.1. Studies addressing protein expression profiles and metabolic abnormalities are underway, as well as studies addressing their ability to differentiate into neurons. This resource of iPS cells can be used as a model for exploring the mechanisms of pathogenesis in DYT1 dystonia.