biostudies-literature00400UnknownCorrea-Vela MSpanish Foundation per Amor a l`Art (FPAA)Instituto de Salud Carlos IIIFundació la Marató de TV3Ministerio de Educación, Cultura y DeporteGeneralitat ValencianaFBXO7 is implicated in the ubiquitin-proteasome system and parkin-mediated mitophagy. FBXO7defects cause a levodopa-responsive parkinsonian-pyramidal syndrome(PPS). METHODS:We investigated the disease molecular bases in a child with PPS and brain iron accumulation. RESULTS:A novel homozygous c.368C>G (p.S123*) FBXO7 mutation was identified in a child with spastic paraplegia, epilepsy, cerebellar degeneration, levodopa nonresponsive parkinsonism, and brain iron deposition. Patient's fibroblasts assays demonstrated an absence of FBXO7 RNA expression leading to impaired proteasome degradation and accumulation of poly-ubiquitinated proteins. CONCLUSION:This novel FBXO7 phenotype associated with impaired proteasome activity overlaps with neurodegeneration with brain iron accumulation disorders.Annals of clinical and translational neurologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC7448169biostudies-literatureImpaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect.PMC74481692014313020143131OP ERDF of Comunitat Valenciana 2014-2020PI18/01319PI18/00147FPU-PhD fellowship FPU 15/00964PROMETEO/2018/135Marce-Grau ADarling ASobrido MJMartinez-Vicente MTello CJenkins ALupo VFernandez-Rodriguez SEspinos CSancho PSanchez-Montanez AMacaya ARamirez-Jimenez LPerez-Duenas BPerez BCorrea-Vela MMontpeyo MHernandez-Vara J40falseImpaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect.FBXO7 is implicated in the ubiquitin-proteasome system and parkin-mediated mitophagy. FBXO7defects cause a levodopa-responsive parkinsonian-pyramidal syndrome(PPS). METHODS:We investigated the disease molecular bases in a child with PPS and brain iron accumulation. RESULTS:A novel homozygous c.368C>G (p.S123*) FBXO7 mutation was identified in a child with spastic paraplegia, epilepsy, cerebellar degeneration, levodopa nonresponsive parkinsonism, and brain iron deposition. Patient's fibroblasts assays demonstrated an absence of FBXO7 RNA expression leading to impaired proteasome degradation and accumulation of poly-ubiquitinated proteins. CONCLUSION:This novel FBXO7 phenotype associated with impaired proteasome activity overlaps with neurodegeneration with brain iron accumulation disorders.2020-01-01T00:00:00Z2020 Aug2020-11-07T11:39:28Z2020-09-04T07:04:55ZS-EPMC74481693276748010.1002/acn3.51095