title: OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology.
abstract: Mutations in the Optic Atrophy 1 gene (OPA1) were first identified in 2000 as the main cause of Dominant Optic Atrophy, a disease specifically affecting the retinal ganglion cells and the optic nerve. Since then, an increasing number of symptoms involving the central, peripheral and autonomous nervous systems, with considerable variations of age of onset and severity, have been reported in OPA1 patients. This variety of phenotypes is attributed to differences in the effects of OPA1 mutations, to the mode of inheritance, which may be mono- or bi-allelic, and eventually to somatic mitochondrial DNA mutations. The diversity of the pathophysiological mechanisms involved in OPA1-related disorders is linked to the crucial role played by OPA1 in the maintenance of mitochondrial structure, genome and function. The neurological expression of these disorders highlights the importance of mitochondrial dynamics in neuronal processes such as dendritogenesis, axonal transport, and neuronal survival. Thus, OPA1-related disorders may serve as a paradigm in the wider context of neurodegenerative syndromes, particularly for the development of novel therapeutic strategies against these diseases.
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Juan Manuel
authors: JM
authors: Chao de la Barca
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Delphine
authors: D
authors: Prunier-Mirebeau
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Patrizia
authors: P
authors: Amati-Bonneau
authors: UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Marc
authors: M
authors: Ferré
authors: INSERM U1051, Institut des Neurosciences, Montpellier, France.
authors: Emmanuelle
authors: E
authors: Sarzi
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Céline
authors: C
authors: Bris
authors: Centre Hospitalier Universitaire, Département d'Ophtalmologie, Angers, France.
authors: Stéphanie
authors: S
authors: Leruez
authors: UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Arnaud
authors: A
authors: Chevrollier
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Valérie
authors: V
authors: Desquiret-Dumas
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Naïg
authors: N
authors: Gueguen
authors: UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France; Centre Hospitalier Universitaire, Département de Neurologie, Angers, France.
authors: Christophe
authors: C
authors: Verny
authors: INSERM U1051, Institut des Neurosciences, Montpellier, France; Centre Hospitalier Universitaire, Centre de référence des affections sensorielles d'origine génétique, Montpellier, France.
authors: Christian
authors: C
authors: Hamel
authors: UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France; Centre Hospitalier Universitaire, Département d'Ophtalmologie, Angers, France; Singapore Eye Research Institute, Duke-NUS, Singapore.
authors: Dan
authors: D
authors: Miléa
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Vincent
authors: V
authors: Procaccio
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Dominique
authors: D
authors: Bonneau
authors: UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
authors: Guy
authors: G
authors: Lenaers
authors: Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France. Electronic address: pareynier@chu-angers.fr.
authors: Pascal
authors: P
authors: Reynier
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D020558:GTP Phosphohydrolases
keywords: Mitochondria; Mitochondrial dynamics; OPA1; Optic neuropathy; Oxidative phosphorylation; Retinal ganglion cells