title: A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability.
abstract: Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red-green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies.
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier Montpellier, France ; PREMMi, CNRS UMR 6214 - INSERM U1083, Département de Biochimie et Génétique, Université d'Angers, CHU d'Angers Angers, France.
authors.forename: Majida
authors.initials: M
authors.lastname: Charif
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier Montpellier, France ; CHRU Montpellier, Service de Neuro-pédiatrie, Hôpital Gui de Chauliac Montpellier, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier Montpellier, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Salime
authors.affiliation: CHRU Montpellier, Centre de Référence pour les Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac Montpellier, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mamouni
authors.affiliation: CHU Bordeaux, Service de Génétique Médicale and Université de Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM) Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier Montpellier, France ; CHRU Montpellier, Centre de Référence pour les Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac Montpellier, France.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.affiliation: Institut des Neurosciences de Montpellier, U1051 de l'INSERM, Université de Montpellier Montpellier, France ; PREMMi, CNRS UMR 6214 - INSERM U1083, Département de Biochimie et Génétique, Université d'Angers, CHU d'Angers Angers, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lenaers
keywords: AFG3L2; OPA1; dominant mutation; optic nerve; retinal ganglion neurons