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

Identification of a novel m.3955G > A variant in MT-ND1 associated with Leigh syndrome.

Mitochondrion 62, 13-23 (2022)
Postprint DOI PMC
Open Access Green
Leigh syndrome (LS) is one of the most common mitochondrial diseases in children, for which at least 90 causative genes have been identified. However, many LS patients have no genetic diagnosis, indicating that more disease-related genes remain to be identified. In this study, we identified a novel variant, m.3955G > A, in mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in two unrelated LS patients, manifesting as infancy-onset frequent seizures, neurodegeneration, elevated lactate levels, and bilateral symmetrical lesions in the brainstem, basal ganglia, and thalamus. Transfer of the mutant mtDNA with m.3955G > A into cybrids disturbed the MT-ND1 expression and CI assembly, followed by remarkable mitochondrial dysfunction, reactive oxygen species production, and mitochondrial membrane potential reduction. Our findings demonstrated the pathogenicity of the novel m.3955G > A variant, and extend the spectrum of pathogenic mtDNA variants.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cybrid Cells ; Leigh Syndrome ; Mt-nd1 ; Novel Mitochondrial Dna Variant; Hereditary Optic Neuropathy; Complex-i Deficiency; Mitochondrial Disease; Mutations; Encephalopathy; Gene
Language english
Publication Year 2022
Prepublished in Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1567-7249
e-ISSN 1872-8278
Journal Mitochondrion
Quellenangaben Volume: 62, Issue: , Pages: 13-23 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503292-001
DOI 10.1016/j.mito.2021.10.002
WOS ID WOS:000717843300002
Scopus ID 85118582265
PubMed ID 34656796
Erfassungsdatum 2021-12-17
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