Details

Autor(en) / Beteiligte

• Xu, Manting
• Kopajtich, Robert
• Elstner, Matthias
• Wang, Zhaoxia
• Liu, Zhimei
• Wang, Junling
• Prokisch, Holger
• Fang, Fang

Titel

Identification of a Novel Variant in MT-CO3 Causing MELAS

Ist Teil von

• Frontiers in genetics, 2021-05, Vol.12, p.638749-638749

Ort / Verlag

Frontiers Media S.A

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.