Leber's Hereditary Optic Neuropathy: A Report on Novel mtDNA Pathogenic Variants.

Leber's hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA); 90% of cases harbor the m.3460G>A, m.11778G>A, and m.14484T>C primary mutations. Here, we report and discuss five families with patients affected by symptomatic LHON, in which we found five novel mtDNA variants. Remarkably, these mtDNA variants are located in complex I genes, though without strong deleterious effect on respiration in cellular models: this finding is likely linked to the tissue specificity of LHON. This study observes that in the case of a strong clinical suspicion of LHON, it is recommended to analyze the whole mtDNA sequence, since new rare mtDNA pathogenic variants causing LHON are increasingly identified.
Competing Interests: CL and VC are involved in LHON clinical trials with Santhera and GenSight Pharmaceuticals, serving also as consultants. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Peverelli, Catania, Marchet, Ciasca, Cammarata, Melzi, Bellino, Fancellu, Lamantea, Capristo, Caporali, La Morgia, Carelli, Ghezzi, Bianchi Marzoli and Lamperti.)