Hereditary neuropathy or pain disorder
Gene: ACOX1
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
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
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
Tag Q1_23_promote_green was removed from gene: ACOX1.
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)
Tag Q1_23_promote_green tag was added to gene: ACOX1.
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)
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