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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cybrid Cells ; Leigh Syndrome ; Mt-nd1 ; Novel Mitochondrial Dna Variant; Hereditary Optic Neuropathy; Complex-i Deficiency; Mitochondrial Disease; Mutations; Encephalopathy; Gene
ISSN (print) / ISBN 1567-7249
e-ISSN 1872-8278
Zeitschrift Mitochondrion
Quellenangaben Band: 62, Heft: , Seiten: 13-23 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)