Author:
Rákosníková Tereza,Kelifová Silvie,Štufková Hana,Lokvencová Kateřina,Lišková Petra,Kousal Bohdan,Honzík Tomáš,Hansíková Hana,Martínek Václav,Tesařová Markéta
Abstract
Leber hereditary optic neuropathy is a primary mitochondrial disease characterized by acute visual loss due to the degeneration of retinal ganglion cells. In this study, we describe a patient carrying a rare missense heteroplasmic variant in MT-ND1, NC_012920.1:m.4135T>C (p.Tyr277His) manifesting with a typical bilateral painless decrease of the visual function, triggered by physical exercise or higher ambient temperature. Functional studies in muscle and fibroblasts show that amino acid substitution Tyr277 with His leads to only a negligibly decreased level of respiratory chain complex I (CI), but the formation of supercomplexes and the activity of the enzyme are disturbed noticeably. Our data indicate that although CI is successfully assembled in the patient’s mitochondria, its function is hampered by the m.4135T>C variant, probably by stabilizing CI in its inactive form. We conclude that the m.4135T>C variant together with a combination of external factors is necessary to manifest the phenotype.
Funder
Ministerstvo Zdravotnictví Ceské Republiky
Univerzita Karlova v Praze
Subject
Genetics (clinical),Genetics,Molecular Medicine
Cited by
1 articles.
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