An ADPRS variant disrupts ARH3 stability and subcellular localization in children with neurodegeneration and respiratory failure.

ABSTRACT: ADP-ribosylation is a post-translational modification involving the transfer of one or more ADP-ribose units from NAD+ to target proteins. Dysregulation of ADP-ribosylation is implicated in neurodegenerative diseases. In this study, genetic testing via exome sequencing was used to identify the underlying disease in two siblings with developmental delay, seizures, progressive muscle weakness, and respiratory failure following an episodic course. This identified a novel homozygous variant in the ADPRS gene (c.545A>G, p.His182Arg) encoding the mono(ADP-ribosyl) hydrolase ARH3, confirming the diagnosis of childhood-onset neurodegeneration with stress-induced ataxia and seizures (CONDSIAS) in these two children. Mechanistically, the ARH3^H182R variant affects a highly conserved residu

SUBMITTER: Bannister M 

PROVIDER: S-EPMC11667697 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature