Inherited white matter disorders

Gene: ACOX1

Green List (high evidence)

ACOX1 (acyl-CoA oxidase 1)
EnsemblGeneIds (GRCh38): ENSG00000161533
EnsemblGeneIds (GRCh37): ENSG00000161533
OMIM: 609751, Gene2Phenotype
ACOX1 is in 12 panels

3 reviews

Ivone Leong (Genomics England Curator)

Comment on mode of inheritance: PMID: 32169171. 3 unrelated patients with the same de novo variant (N237S) with a progressive disease. Age of onset is between 3-12 years old (cf to AR patients 0-3 years old), disease course is progressive (AR patients, early onset and severe) white matter demyelination is progressive, sensorineural hearing loss and ataxia. Authors found that the variant increased levels of ACOX1 protein and function which increased levels of ROS in glia of Drosphila and mouse Schwann cells leading to glial degeneration. The authors suggested that the variant caused a GOF effect. AD causes Mitchell syndrome (OMIM:618960) and AR causes Peroxisomal acyl-CoA oxidase deficiency (OMIM:264470).

Therefore, MOI should be changed from Biallelic to Both monoallelic and biallelic (but biallelic mutations cuase a more severe disease form).
Created: 2 Jul 2021, 10:46 a.m. | Last Modified: 5 Jul 2021, 8:54 a.m.
Panel Version: 1.129

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
General Leukodystrophy & Mitochondrial Leukoencephalopathy

Publications

  • Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648

Variants in this GENE are reported as part of current diagnostic practice

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in G2P. Numerous variants reported in this phenotype.
Created: 7 Jul 2016, 7:03 a.m.
Comment on list classification: Provisionally accepted by UKGTN for Combined leukodystrophy/mitochondrial leukoencephalopathy 94-gene panel (Ian Berry)
Created: 7 Jul 2016, 7:01 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Peroxisomal acyl-CoA oxidase deficiency 264470
  • General Leukodystrophy & Mitochondrial Leukoencephalopathy
  • Mitchell syndrome, OMIM:618960
OMIM
609751
Clinvar variants
Variants in ACOX1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Jul 2021, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

2 Jul 2021, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648

2 Jul 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitchell syndrome, OMIM:618960

6 Oct 2016, Gel status: 4

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

6th Oct 2016: Panel promoted to version 1 after expert review and input, further curation and clinical input.

4 Aug 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for ACOX1 were set to Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy

4 Aug 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648

4 Aug 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648

7 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

7 Jul 2016, Gel status: 4

Set publications

Sarah Leigh (Genomics England Curator)

Publications for ACOX1 were set to 25655951; 11815777; 17458872

7 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for ACOX1 were set to Peroxisomal acyl-CoA oxidase deficiency 264470

7 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

7 Jul 2016, Gel status: 4

Upload gene information

Sarah Leigh (Genomics England Curator)

ACOX1 was added to Inherited white matter disorderspanel. Sources: Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,UKGTN

19 May 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

ACOX1 was created by ellenmcdonagh

19 May 2016, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ACOX1 was added to Inherited white matter disorderspanel. Sources: Illumina TruGenome Clinical Sequencing Services