Monogenic hearing loss

Gene: ACOX1

Green List (high evidence)

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: 3.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mitchell syndrome, OMIM:618960

Publications

• 32169171