Hereditary neuropathy or pain disorder
Gene: ACOX1EnsemblGeneIds (GRCh38): ENSG00000161533
EnsemblGeneIds (GRCh37): ENSG00000161533
OMIM: 609751, Gene2Phenotype
ACOX1 is in 12 panels
3 reviews
Sarah Leigh (Genomics England Curator)
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 6:06 p.m. | Last Modified: 10 Oct 2023, 6:06 p.m.
Panel Version: 3.58
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mafalda Gomes (Genomics England Curator)
Chung et al. (2020) report 3 unrelated cases with a recurrent de novo variant (N237S). These patients exhibit a severe loss of Schwann cells and neurons, and are affected with progressive myeloneuropathy with sensorineural hearing loss (onset 3-12 years). This paper provides evidence for a new mechanism of disease for ACOX1, heterozygous gain-of-function variant causing autosomal dominant disease, in contrast to the already described autosomal recessive peroxisomal disorders, caused by a deficiency of ACOX1. The study also includes functional studies that show that the N237S variant increases levels of the protein, resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.Created: 20 Jan 2023, 11:16 a.m. | Last Modified: 20 Jan 2023, 11:16 a.m.
Panel Version: 2.9
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Mitchell syndrome, OMIM:618960
Publications
Zornitza Stark (Australian Genomics)
Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. By contrast, bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apnoeic spells, delayed psychomotor development, and neurologic regression.
Sources: LiteratureCreated: 3 Aug 2020, 10:52 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Mitchell syndrome, MIM# 618960
Publications
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- NHS GMS
- Expert Review Green
- Phenotypes
-
- Mitchell syndrome, MIM# 618960
- OMIM
- 609751
- Clinvar variants
- Variants in ACOX1
- Penetrance
- None
- Publications
- Panels with this gene
-
- Monogenic hearing loss
- Early onset or syndromic epilepsy
- Inherited white matter disorders
- Fetal anomalies
- Hereditary neuropathy or pain disorder
- Undiagnosed metabolic disorders
- White matter disorders and cerebral calcification - narrow panel
- Intellectual disability
- Childhood onset dystonia, chorea or related movement disorder
- Likely inborn error of metabolism
- Peroxisomal disorders
- DDG2P
History Filter Activity
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q1_23_promote_green was removed from gene: ACOX1.
Added New Source, Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source Expert Review Green was added to ACOX1. Source NHS GMS was added to ACOX1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Added Tag
Mafalda Gomes (Genomics England Curator)Tag Q1_23_promote_green tag was added to gene: ACOX1.
Added New Source, Set mode of inheritance, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Amber was added to ACOX1. Mode of inheritance for gene ACOX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Rating Changed from No List (delete) to Amber List (moderate evidence)
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Zornitza Stark (Australian Genomics)gene: ACOX1 was added gene: ACOX1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACOX1 were set to 32169171 Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MIM# 618960 Review for gene: ACOX1 was set to GREEN gene: ACOX1 was marked as current diagnostic