Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy

Charif, Majida, Chevrollier, Arnaud, Gueguen, Naïg, Bris, Céline, Goudenège, David, Desquiret-Dumas, Valérie, Leruez, Stéphanie, Colin, Estelle, Meunier, Audrey, Vignal, Catherine, Smirnov, Vasily, Defoort-Dhellemmes, Sabine, Drumare Bouvet, Isabelle, Goizet, Cyril, Votruba, Marcela ORCID:, Jurkute, Neringa, Yu-Wai-Man, Patrick, Tagliavini, Francesca, Caporali, Leonardo, La Morgia, Chiara, Carelli, Valerio, Procaccio, Vincent, Zanlonghi, Xavier, Meunier, Isabelle, Reynier, Pascal, Bonneau, Dominique, Amati-Bonneau, Patrizia and Lenaers, Guy 2020. Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy. Neurology Genetics 6 (3) , e428. 10.1212/NXG.0000000000000428

[thumbnail of e428.full.pdf] PDF - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (747kB)


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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Wolters Kluwer Health on behalf of the American Academy of Neurology
ISSN: 2376-7839
Date of First Compliant Deposit: 3 July 2020
Date of Acceptance: 6 April 2020
Last Modified: 05 May 2023 16:51

Citation Data

Cited 19 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics