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BACKGROUND: The most likely genetic cause of X-linked dystonia-parkinsonism, a neurodegenerative movement disorder endemic to the Philippines, is a 2672-bp-long retrotransposon insertion in intron 32 of the TAF1 gene. The objectives of this study were to investigate whether (1) TAF1 expression is altered in induced pluripotent stem cells and differentiated neuronal models and (2) excision of the retrotransposon insertion restores normal TAF1 expression. METHODS: Expression of TAF1 and its neuronal isoform were determined in induced pluripotent stem cells and in induced pluripotent stem cell-derived cortical neurons and spiny projection neurons using quantitative PCR. Genome editing-based excision of the retrotransposon insertion was performed on induced pluripotent stem cells from 3 X-linked dystonia-parkinsonism patients. Edited and unedited induced pluripotent stem cells from X-linked dystonia-parkinsonism patients and controls were differentiated into cortical neurons and spiny projection neurons, and TAF1 expression was compared across groups. RESULTS: TAF1 was reduced in patient-derived induced pluripotent stem cells (P 

Original publication

DOI

10.1002/mds.27441

Type

Journal article

Journal

Mov Disord

Publication Date

07/2018

Volume

33

Pages

1108 - 1118

Keywords

dystonia, genome editing, induced pluripotent stem cells, parkinsonism, Adult, Cells, Cultured, Cerebral Cortex, Dystonic Disorders, Female, Gene Editing, Genetic Diseases, X-Linked, Growth Differentiation Factor 3, Histone Acetyltransferases, Humans, Induced Pluripotent Stem Cells, Male, Middle Aged, Nanog Homeobox Protein, Nerve Tissue Proteins, Octamer Transcription Factor-3, RNA, Messenger, SOXB1 Transcription Factors, TATA-Binding Protein Associated Factors, Transcription Factor TFIID, Transfection, Tubulin