biostudies-literatureMartinez-Rubio DSpanish Ministry of Science and InnovationSpanish Ministry of Economy and CompetitivenessFundació la Marató de TV3Generalitat ValencianaEuropean Regional Development Fund3897-3913https://www.ebi.ac.uk/biostudies/studies/S-EPMC9652108biostudies-literatureUnknown31(22)Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial computHuman molecular geneticsProtein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3.PMC96521082014313020143131PI18/00147PRE2018-083562RyC-2014-16410PI21/00103SAF2017-89020-RPROMETEO/2018/135Navarro-Gonzalez CMartinez-Rubio DGorria-Redondo NJenkins ARodriguez-Prieto AEspinos CSancho PFazzari PAguilera-Albesa SPerez-Duenas BMarco-Marin CMiquel-Leal JSoriano-Navarro MHernandez AfalseProtein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3.Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial comput2022-01-01T00:00:00Z2022 Nov2026-05-28T00:32:54.189Z2025-04-06T01:50:46.705ZS-EPMC96521083576688210.1093/hmg/ddac146