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| Intellectual disability v11.42 | ACO2 | Ida Ertmanska commented on gene: ACO2: Comment on mode of inheritance: There are numerous patients reported with both mono- and bi-allelic variants in ACO2. Individuals with heterozygous ACO2 variants present with isolated optic atrophy, while those with biallelic variants may present with either syndromic or non-syndromic optic atrophy. Syndromic presentation usually involves cerebellar-retinal degeneration, ataxia, seizures, ID, and developmental delays. Hence, the MOI should be changed to BIALLELIC, autosomal or pseudoautosomal for Intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.42 | ACO2 | Ida Ertmanska edited their review of gene: ACO2: Changed publications to: 22405087, 25351951, 31106992, 32519519, 34056600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.42 | ACO2 |
Ida Ertmanska changed review comment from: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. PMID: 22405087 Spiegel et al., 2012 Studied eight individuals from two unrelated families of Arab Muslim origin who presented at 2–6 months of age with truncal hypotonia and athetosis, seizure disorder, profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Six individuals older than 2 years were profoundly intellectually disabled. All patients were homozygous for ACO2 p.Ser112Arg. Method: homozygosity mapping and WES. Ten parents and one of the healthy sibs were confirmed to be heterozygous. ACO2 is associated with AR Infantile cerebellar-retinal degeneration, OMIM:614559 and AD Optic atrophy 9. OMIM:616289 in OMIM (accesssed 8th Oct 2026).; to: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. PMID: 31106992 Fukada et al., 2019 Report of a Japanese female patient with progressive cerebellar and cerebral atrophy, hypotonia, ataxia, seizure disorder, developmental delay, ophthalmological abnormalities and hearing loss. WES detected comp het missense variants (c.1534G>A, p.Asp512Asn and c.1997G>C, p.Gly666Ala) in ACO2. Parents were healthy and unrelated, confirmed to be het for a variant each. PMID: 25351951 Metodiev et al., 2014 Study of 5 patients from 3 unrelated families with homozygous or compound heterozygous missense and frameshift mutations in ACO2, with either isolated or syndromic optic neuropathy. PMID: 22405087 Spiegel et al., 2012 Studied eight individuals from two unrelated families of Arab Muslim origin who presented at 2–6 months of age with truncal hypotonia and athetosis, seizure disorder, profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Six individuals older than 2 years were profoundly intellectually disabled. All patients were homozygous for ACO2 p.Ser112Arg. Method: homozygosity mapping and WES. Ten parents and one of the healthy sibs were confirmed to be heterozygous. ACO2 is associated with AR Infantile cerebellar-retinal degeneration, OMIM:614559 and AD Optic atrophy 9. OMIM:616289 in OMIM (accesssed 8th Oct 2026). |
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| Intellectual disability v11.42 | ACO2 |
Ida Ertmanska changed review comment from: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. PMID: 22405087 Spiegel et al., 2012 Studied eight individuals from two unrelated families of Arab Muslim origin who presented at 2–6 months of age with truncal hypotonia and athetosis, seizure disorder, profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Six individuals older than 2 years were profoundly intellectually disabled. All patients were homozygous for ACO2 p.Ser112Arg. Method: homozygosity mapping and WES. Ten parents and one of the healthy sibs were confirmed to be heterozygous.; to: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. PMID: 22405087 Spiegel et al., 2012 Studied eight individuals from two unrelated families of Arab Muslim origin who presented at 2–6 months of age with truncal hypotonia and athetosis, seizure disorder, profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Six individuals older than 2 years were profoundly intellectually disabled. All patients were homozygous for ACO2 p.Ser112Arg. Method: homozygosity mapping and WES. Ten parents and one of the healthy sibs were confirmed to be heterozygous. ACO2 is associated with AR Infantile cerebellar-retinal degeneration, OMIM:614559 and AD Optic atrophy 9. OMIM:616289 in OMIM (accesssed 8th Oct 2026). |
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| Intellectual disability v11.42 | ACO2 | Ida Ertmanska Tag Q4_26_MOI tag was added to gene: ACO2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.42 | ACO2 | Ida Ertmanska Publications for gene: ACO2 were set to 22405087; 25351951; 34056600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.41 | ACO2 | Ida Ertmanska edited their review of gene: ACO2: Changed publications to: 22405087, 32519519, 34056600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.41 | ACO2 |
Ida Ertmanska changed review comment from: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2.; to: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. PMID: 22405087 Spiegel et al., 2012 Studied eight individuals from two unrelated families of Arab Muslim origin who presented at 2–6 months of age with truncal hypotonia and athetosis, seizure disorder, profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Six individuals older than 2 years were profoundly intellectually disabled. All patients were homozygous for ACO2 p.Ser112Arg. Method: homozygosity mapping and WES. Ten parents and one of the healthy sibs were confirmed to be heterozygous. |
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| Intellectual disability v11.41 | ACO2 |
Ida Ertmanska changed review comment from: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort.; to: PMID: 34056600 Charif et al., 2021 Study identified 61 cases harbouring variants in ACO2. 50/61 harboured heterozygous ACO2 variants. 52 individuals had isolated optic atrophy. "27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy (...) with a single case showing hearing loss (P38) and two cases showing a late-onset cerebellar ataxia (P19 and P53)." However, extraocular features in the dominant cases were not consistent and mostly did not match the AR Infantile cerebellar-retinal degeneration disease entity associated with ACO2 - probably incidental findings. P19 - somewhat consistent - het for ACO2 p.Gly463Arg and had cerebellar ataxia. Among recessive cases, 1 individual had epilepsy with onset at 22 yrs (comp het for ACO2 c.36+5delG and p.(Gly240Ala)). Another patient presented with kinetic and static cerebellar syndrome with cerebellar atrophy; episode of dysarthria at 45 y - comp het for ACO2 p.(Leu74Val) and p.(Glu464*). No mention of intellectual disability in this cohort. PMID: 32519519 Blackburn et al., 2020 Report of five patients with biallelic pathogenic variants in ACO2: Case 1 & 2 - Two sibs with relatively mild symptoms presented with episodic ataxia, mild developmental delays, severe dysarthria, and behavioral abnormalities. Case 3 - proband presented with the classic form with cerebellar hypoplasia, ataxia, seizures, moderate‐to‐severe intellectual disability, optic atrophy, and retinitis pigmentosa. Case 4 - proband demonstrated a spinal muscular atrophy‐like presentation with severe neonatal hypotonia, diminished reflexes, and poor respiratory drive, leading to ventilator dependence until death at the age of 9 months. Case 5 - proband presented with ataxia, severe developmental and motor delays, and seizures; developed severe progressive spastic quadriplegia. Mostly missense variants; Case 5 had biallelic frameshift variants in ACO2. |
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| Intellectual disability v11.41 | ACO2 | Ida Ertmanska reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34056600; Phenotypes: Infantile cerebellar-retinal degeneration, OMIM:614559, Optic atrophy 9. OMIM:616289; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v4.53 | ACO2 | Arina Puzriakova Tag Q2_22_MOI was removed from gene: ACO2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v4.53 | ACO2 | Arina Puzriakova commented on gene: ACO2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v4.52 | ACO2 |
Arina Puzriakova 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 |
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| Intellectual disability v3.1593 | ACO2 | Sarah Leigh Tag Q2_22_MOI tag was added to gene: ACO2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1593 | ACO2 |
Sarah Leigh commented on gene: ACO2: New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed. Tom Cullup (Great Ormond Street Hospital), 17 Feb 2022 |
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| Intellectual disability v3.1593 | ACO2 | Sarah Leigh reviewed gene: ACO2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1593 | ACO2 | Sarah Leigh Publications for gene: ACO2 were set to 22405087; 25351951 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.968 | ACO2 | Arina Puzriakova Phenotypes for gene: ACO2 were changed from INFANTILE CEREBELLAR-RETINAL DEGENERATION to Infantile cerebellar-retinal degeneration, OMIM:614559; Infantile cerebellar-retinal degeneration, MONDO:0013802 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.468 | ACO2 | Louise Daugherty Source Victorian Clinical Genetics Services was added to ACO2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||