1. Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.
- Author
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Ganetzky RD, Markhard AL, Yee I, Clever S, Cahill A, Shah H, Grabarek Z, To TL, and Mootha VK
- Subjects
- Humans, Male, Adenosine Triphosphate metabolism, Diseases in Twins genetics, Diseases in Twins metabolism, Fibroblasts metabolism, Mitochondria metabolism, Mutation, Twins, Monozygotic genetics, Mitochondrial Diseases congenital, Mitochondrial Diseases genetics, Mitochondrial Diseases metabolism, Mitochondrial Proton-Translocating ATPases genetics, Mitochondrial Proton-Translocating ATPases metabolism, Oxidative Phosphorylation, Oxygen Consumption genetics, Oxygen Consumption physiology
- Abstract
We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in ATP5F1B , which encodes the β subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, resulting in high rates of mitochondrial respiration. Expression of the mutant allele in human cell lines recapitulates this phenotype. These data support an autosomal dominant mitochondrial uncoupling syndrome with hypermetabolism. (Funded by the National Institutes of Health.)., (Copyright © 2022 Massachusetts Medical Society.)
- Published
- 2022
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