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A Novel m.4349c>T Mutation Causes Mitochondrial Encephalopathy by Disturbing Translation Machinery and Mitochondrial Function
31 Pages Posted: 28 Jul 2020
More...Abstract
Background: Mitochondrial diseases are a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA, among which, mutations in mitochondrial tRNA genes possessing prominent status. In most of the cases, however, the detailed molecular pathogenesis of these tRNA gene mutations remains unclear.
Methods: We performed the clinical emulation, muscle histochemistry, northern blotting analysis of tRNA levels, biochemical measurement of respiratory chain complex activities and mitochondrial respirations in muscle tissue and cybrid cells.
Findings: We found a novel m.4349C>T mutation in mitochondrial tRNAGln gene in a patient present with encephalopathy, epilepsy and deafness. We demonstrated molecular pathomechanisms of this mutation. This mutation firstly disturbed the translation machinery of mitochondrial tRNAGln and impaired mitochondrial respiratory chain complex activities, followed by remarkable mitochondrial dysfunction and ROS production.
Interpretation: This study illustrated the pathogenicity of a novel m.4349C>T mutation and provided a better understanding of the phenotype associated with mutations in mitochondrial tRNAGln.
Funding Statement: This study was supported by the National Natural Science Foundation of China (No.81701237 and 81671235), People's benefit project of science and technology in Qingdao (16-6-2-1-nsh) and the Taishan Scholars Program of Shandong Province.
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: All procedures performed in studies involving human participant were in accordance with the ethical standards and the study was approved by the local ethics committee. Informed consent was obtained from the patient included in the study.
Keywords: mitochondrial disease; m.4349C>T mutation; mitochondrial tRNAGln
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