Optic neuropathy
Gene: ACO2The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 1:02 p.m. | Last Modified: 30 Jan 2023, 1:02 p.m.
Panel Version: 3.7
PMID: 34056600 reports 61 cases of genetically unsolved inherited optic neuropathies who were harbouring variants in ACO2, of which 50 carried dominant variants (the remaining 11 cases were biallelic). The authors state that this is the first report of monoallelic pathogenic ACO2 variants resulting in dominant optic atrophy.Created: 24 May 2022, 5:01 p.m. | Last Modified: 26 May 2022, 12:43 p.m.
Panel Version: 2.69
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed.Created: 17 Feb 2022, 4:43 p.m. | Last Modified: 17 Feb 2022, 4:43 p.m.
Panel Version: 2.56
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Optic atrophy 9, 616289; optic atrophy, nystagmus; Infantile cerebellar-retinal degeneration
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Five patients (from 3 different families) with isolated or syndromic
optic neuropathy were all found to be homozygous or compound heterozygous for missense or frameshift variants in the ACO2 gene (PMID: 25351951). Fibroblasts from all patients showed a decrease in ACO2 activity. A founder variant (p.Ser112Arg NP_001089.1, c.336C>G NM_001098.2) has also been reported in patients with infantile cerebellar-retinal degeneration (which includes optic atrophy) from 2 unrelated families of Arab Muslim origin (PMID: 22405087). All 8 affected individuals were homozygous for the variant. Additional in vitro assays were carried out to support the functional significance of the variant.Created: 7 Sep 2016, 10:54 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Optic atrophy 9; 616289
Publications
Tag Q2_22_MOI was removed from gene: ACO2. Tag Q2_22_NHS_review was removed from gene: ACO2.
Source NHS GMS was added to ACO2. Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q2_22_MOI tag was added to gene: ACO2. Tag Q2_22_NHS_review tag was added to gene: ACO2.
Publications for gene: ACO2 were set to 25351951; 22405087
Phenotypes for gene: ACO2 were changed from Optic atrophy 9; 616289; optic atrophy, nystagmus; Infantile cerebellar-retinal degeneration to Infantile cerebellar-retinal degeneration, OMIM:614559; Infantile cerebellar-retinal degeneration, MONDO:0013802; ?Optic atrophy 9, OMIM:616289; Optic atrophy 9, MONDO:0014571
Source London North GLH was added to ACO2. Rating Changed from Green List (high evidence) to Green List (high evidence)
13.09.2016: 'Inherited optic neuropathies' was removed as a relevant disorder from the Posterior segment abnormalities gene panel (version 1.9) and this panel was approved to live. It has been internally reviewed and revised based on evidence available for each gene, and was promoted to version 1 to be used for analysis.
This gene has been classified as Green List (High Evidence).
Phenotypes for ACO2 were set to Optic atrophy 9; 616289; optic atrophy, nystagmus; Infantile cerebellar-retinal degeneration
Publications for ACO2 were set to 25351951;22405087
This gene has been classified as Green List (High Evidence).
Phenotypes for ACO2 were set to Optic atrophy 9; 616289; optic atrophy, nystagmus
This gene has been classified as Red List (Low Evidence).
ACO2 was added to Inherited optic neuropathiespanel. Sources: Other
ACO2 was created by ellenmcdonagh