Optic Atrophy

Gene: OPA3

Green List (high evidence)

Mutations in OPA3 can impart distinct phenotypes carried through dominant or recessive inheritance patterns but with the common universal feature of optic atrophy, underscoring the critical and susceptible role of mitochondrial health in optic nerve function (PMID: 31928268).

Intra- and interfamilial variability in age of onset and presenting symptoms was observed (PMID: 25159689).

Loss of function is a known mechanism of disease in this gene and is associated with 3-methylglutaconic aciduria, type III (MIM#258501) (PMID: 31928268). The precise mechanism for missense is unknown, however it was suggested they could cause dominant Optic atrophy 3 with cataract (MIM#165300) through either dominant negative or gain of function mechanism (PMID: 31119193).

Two transcripts: transcript variant 2 (exon 1 plus exon 2 [NM_025136.3]) and transcript variant 1 (exon 1 plus exon 3 [NM_001017989.2]), where transcript 2 is the predominant one in most tissues.

Created: 27 Jan 2021, 12:21 a.m. | Last Modified: 27 Jan 2021, 12:21 a.m.

Panel Version: 0.117

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD

Publications

• 25159689
• 31119193
• 31928268

Mode of pathogenicity
Other