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A high mutation load of m.14597A>G in MT-ND6 causes Leigh syndrome
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Abstract Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder associated with mitochondrial deficiency. m.14597A>G (p.Ile26Thr) in the MT-ND6 gene was reported to cause Leberʼs hereditary optic neuropathy (LHON) or dementia/dysarthria. In previous reports, less than 90% heteroplasmy was shown to result in adult-onset disease. Here, by whole mitochondrial sequencing, we identified m.14597A>G mutation of a patient with LS. PCR–RFLP analysis on fibroblasts from the patient revealed a high mutation load (> 90% heteroplasmy). We performed functional assays using cybrid cell models generated by fusing mtDNA-less rho0 HeLa cells with enucleated cells from patient fibroblasts carrying the m.14597A>G variant. Cybrid cell lines bearing the m.14597A>G variant exhibited severe effects on mitochondrial complex I activity. Additionally, impairment of cell proliferation, decreased ATP production and reduced oxygen consumption rate were observed in the cybrid cell lines bearing the m.14597A>G variant when the cells were metabolically stressed in medium containing galactose, indicating mitochondrial respiratory chain defects. These results suggest that a high mutation load of m.14597A>G leads to LS via a mitochondrial complex I defect, rather than LHON or dementia/dysarthria.
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2a76a814c3ba4c25adefbc26eb47bb7d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41598-021-90196-5