Inherited white matter disorders
Gene: ACOX1Comment 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
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
General Leukodystrophy & Mitochondrial Leukoencephalopathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
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.
Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitchell syndrome, OMIM:618960 to Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470; Mitchell syndrome, OMIM:618960; General Leukodystrophy & Mitochondrial Leukoencephalopathy
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
Publications for gene: ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648
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
6th Oct 2016: Panel promoted to version 1 after expert review and input, further curation and clinical input.
Phenotypes for ACOX1 were set to Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy
Publications for ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648
Publications for ACOX1 were set to 25655951; 11815777; 17458872; Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648
This gene has been classified as Green List (High Evidence).
Publications for ACOX1 were set to 25655951; 11815777; 17458872
Phenotypes for ACOX1 were set to Peroxisomal acyl-CoA oxidase deficiency 264470
This gene has been classified as Green List (High Evidence).
ACOX1 was added to Inherited white matter disorderspanel. Sources: Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,UKGTN
ACOX1 was added to Inherited white matter disorderspanel. Sources: Illumina TruGenome Clinical Sequencing Services
ACOX1 was created by ellenmcdonagh