Clinical and Genetic Spectrum of ACO2-Linked Dominant Optic Atrophy.
Patients with ACO2-linked dominant optic atrophy have moderately impaired vision.
Clinical and Genetic Spectrum of ACO2-Linked Dominant Optic Atrophy.
IMPORTANCE: Aconitase 2 (ACO2) gene variants are one of the most frequent causes of dominant optic atrophy (dominant optic atrophy).
To characterize the clinical and genetic spectrum of ACO2-related dominant optic atrophy and evaluate genotype-phenotype correlations.
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case series to describe the ophthalmological examination of novel dominant optic atrophy cases with a heterozygous ACO2 variant.
Data for 55 patients (median [IQR] age at diagnosis for 45 patients, 24 [8-51] years; 33 male [67%]) from 37 families with ACO2 variants were compiled.
Four patients exhibited retinal abnormalities: 3 displayed a foveopathy, and 1 had retinitis pigmentosa.
There were 12 previously unreported variants (to the authors' knowledge), including the deletion of ACO2 exon 9.
No correlation between BCVA and sex, age at diagnosis (Spearman ρ = -0.19; 95% CI, -0.45 to 0.07), or variant type (Kruskal-Wallis test P =.33) was found, but there was a correlation between BCVA and retinal nerve fiber layer (Spearman ρ = -0.74; 95% CI, -0.85 to -0.54), ganglion cell layer (Spearman ρ = -0.60; 95% CI, -0.79 to -0.30), and MD (Spearman ρ = -0.65; 95% CI, -0.89 to -0.31).
Results of this case series reveal the high clinical heterogeneity among patients with ACO2-related dominant optic atrophy and demonstrated that some of these patients can also exhibit retinal abnormalities.
In addition, there was a deletion of an entire ACO2 exon, emphasizing the potential importance of searching for large genomic rearrangements in patients without a molecular diagnosis.
These findings support further studies to explain clinical variability, as no genotype-phenotype correlation was encountered.