Charif, M;
Chevrollier, A;
Gueguen, N;
Bris, C;
Goudenège, D;
Desquiret-Dumas, V;
Leruez, S;
... Lenaers, G; + view all
(2020)
Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.
Neurology Genetics
, 6
(3)
, Article e428. 10.1212/NXG.0000000000000428.
Preview |
Text
Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.pdf - Published Version Download (659kB) | Preview |
Abstract
Objective: To improve the genetic diagnosis of dominant optic atrophy (DOA), the most frequently inherited optic nerve disease, and infer genotype-phenotype correlations. Methods: Exonic sequences of 22 genes were screened by new-generation sequencing in patients with DOA who were investigated for ophthalmology, neurology, and brain MRI. Results: We identified 7 and 8 new heterozygous pathogenic variants in SPG7 and AFG3L2. Both genes encode for mitochondrial matricial AAA (m-AAA) proteases, initially involved in recessive hereditary spastic paraplegia type 7 (HSP7) and dominant spinocerebellar ataxia 28 (SCA28), respectively. Notably, variants in AFG3L2 that result in DOA are located in different domains to those reported in SCA28, which likely explains the lack of clinical overlap between these 2 phenotypic manifestations. In comparison, the SPG7 variants identified in DOA are interspersed among those responsible for HSP7 in which optic neuropathy has previously been reported. Conclusions: Our results position SPG7 and AFG3L2 as candidate genes to be screened in DOA and indicate that regulation of mitochondrial protein homeostasis and maturation by m-AAA proteases are crucial for the maintenance of optic nerve physiology.
| Type: | Article |
|---|---|
| Title: | Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/NXG.0000000000000428 |
| Publisher version: | https://doi.org/10.1212/NXG.0000000000000428 |
| Language: | English |
| Additional information: | Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
| Keywords: | Optic nerve, Mitochondrial disorders, Spinocerebellar ataxia, Visual loss |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10103658 |
Archive Staff Only
 |
View Item |
