Cristina Ugalde

Abstract Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes.

1Cardiovascular and Metabolic Diseases, Duke-NUS Medical School, Singapore, Singapore 2Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA 3Department of Biochemistry and Pharmacology, The Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia 4Functional Proteomics, Institute of Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany 5Duke Molecular Physiology Institute, Duke University,...

Abstract Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT.