Generation and characterization of a zebrafish gain-of-function ACOX1 Mitchell disease model.

ABSTRACT:

Background

Mitchell syndrome is a rare, neurodegenerative disease caused by an ACOX1 gain-of-function mutation (c.710A>G; p.N237S), with fewer than 20 reported cases. Affected patients present with leukodystrophy, seizures, and hearing loss. ACOX1 serves as the rate-limiting enzyme in peroxisomal beta-oxidation of very long-chain fatty acids. The N237S substitution has been shown to stabilize the active ACOX1 dimer, resulting in dysregulated enzymatic activity, increased oxidative stress, and glial damage. Mitchell syndrome lacks a vertebrate model, limiting insights into the pathophysiology of ACOX1-driven white matter damage and neuroinflammatory insults.

Methods

We report a patient presenting with rapidly progressive white matter damage and neurological decline, who was e

SUBMITTER: Raas Q 

PROVIDER: S-EPMC10864527 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature