Ataxia - paediatric

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 (PMID: 31928268). There is intra- and interfamilial variability in age of onset and presenting symptoms (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: 29 Jan 2021, midnight | Last Modified: 29 Jan 2021, midnight

Panel Version: 0.6119

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