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Xu, M. ; Kopajtich, R. ; Elstner, M.* ; Wang, Z.* ; Liu, Z.* ; Wang, J.* ; Prokisch, H. ; Fang, F.*

Identification of a novel variant in MT-CO3 causing MELAS.

Front. Genet. 12:638749 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial disease. Most cases of MELAS are caused by the m.3243A > G variant in the MT-TL1 gene encoding tRNALeu((UUR)). However, the genetic cause in 10% of patients with MELAS is unknown. We investigated the pathogenicity of the novel mtDNA variant m.9396G > A/MT-CO3 (p.E64K), which affects an extremely conserved amino acid in the CO3 subunit of mitochondrial respiratory chain (MRC) complex IV (CIV) in a patient with MELAS. Biochemical assays of a muscle biopsy confirmed remarkable CIV deficiency, and pathological examination showed ragged red fibers and generalized COX non-reactive muscle fibers. Transfer of the mutant mtDNA into cybrids impaired CIV assembly, followed by remarkable mitochondrial dysfunction and ROS production. Our findings highlight the pathogenicity of a novel m.9396G > A variant and extend the spectrum of pathogenic mtDNA variants.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Melas ; Novel Mitochondrial Dna Variant ; Mt-co3 Gene ; Complex Iv Of Respiratory Chain ; Mitochondrial Diseases; Stroke-like-episodes; Mitochondrial; Encephalopathy; Mutations; Disease; Family; Gene
ISSN (print) / ISBN 1664-8021
e-ISSN 1664-8021
Journal Frontiers in Genetics
Quellenangaben Volume: 12, Issue: , Pages: , Article Number: 638749 Supplement: ,
Publisher Frontiers
Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Grants European Joint Programme on Rare Diseases project GENOMIT
Horizon 2020 through the ERA PerMed project PerMiM
German BMBF through the ERA PerMed project PerMiM
National Natural Science Foundation of China
Capital Health Research and Development Fund