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

Autor:	Peverelli L; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy.; Neuromuscular and Rare Disease Unit, Department of Neuroscience, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy., Catania A; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy., Marchet S; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy., Ciasca P; Neuro-Ophthalmology Service and Ocular Electrophysiology Laboratory, Department of Ophthalmology, Scientific Institute Auxologico Capitanio Hospital, Milan, Italy., Cammarata G; Neuro-Ophthalmology Service and Ocular Electrophysiology Laboratory, Department of Ophthalmology, Scientific Institute Auxologico Capitanio Hospital, Milan, Italy., Melzi L; Neuro-Ophthalmology Service and Ocular Electrophysiology Laboratory, Department of Ophthalmology, Scientific Institute Auxologico Capitanio Hospital, Milan, Italy., Bellino A; Neuromuscular Disorders Unit, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy., Fancellu R; Neurology Unit, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ospedale Policlinico San Martino, Genoa, Italy., Lamantea E; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy., Capristo M; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica, Bologna, Italy., Caporali L; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica, Bologna, Italy., La Morgia C; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica, Bologna, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Carelli V; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica, Bologna, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Ghezzi D; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Bianchi Marzoli S; Neuro-Ophthalmology Service and Ocular Electrophysiology Laboratory, Department of Ophthalmology, Scientific Institute Auxologico Capitanio Hospital, Milan, Italy., Lamperti C; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Neurologico Carlo Besta, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2021 Jun 09; Vol. 12, pp. 657317. Date of Electronic Publication: 2021 Jun 09 (Print Publication: 2021).
DOI:	10.3389/fneur.2021.657317
Abstrakt:	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.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu