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AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.
- Source :
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American journal of ophthalmology [Am J Ophthalmol] 2024 Jun; Vol. 262, pp. 114-124. Date of Electronic Publication: 2024 Jan 24. - Publication Year :
- 2024
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Abstract
- Purpose: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA.<br />Design: Cross-sectional study.<br />Methods: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method.<br />Results: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients.<br />Conclusions: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Female
Humans
Male
Middle Aged
Young Adult
ATP-Dependent Proteases genetics
ATP-Dependent Proteases metabolism
Cross-Sectional Studies
Genetic Association Studies
Mitochondrial Proteins genetics
Mutation
Nerve Fibers pathology
Phenotype
Aconitate Hydratase genetics
ATPases Associated with Diverse Cellular Activities genetics
GTP Phosphohydrolases genetics
Optic Atrophy, Autosomal Dominant genetics
Optic Atrophy, Autosomal Dominant physiopathology
Optic Atrophy, Autosomal Dominant diagnosis
Retinal Ganglion Cells pathology
Tomography, Optical Coherence
Visual Acuity physiology
Visual Fields physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1891
- Volume :
- 262
- Database :
- MEDLINE
- Journal :
- American journal of ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 38278202
- Full Text :
- https://doi.org/10.1016/j.ajo.2024.01.011