Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect

Correa-Vela, M.; Lupo, V.; Montpeyo, M.; Sancho, P.; Marce-Grau, A.; Hernandez-Vara, J.; Darling, A.; Jenkins, A.; Fernandez-Rodriguez, S.; Tello, C.; Ramirez-Jimenez, L.; Perez, B.; Sanchez-Montanez, A.; Macaya, A.; Sobrido Gómez, María Jesús; Martinez-Vicente, M.; Perez-Duenas, B.; Espinos, C.
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URI: http://hdl.handle.net/20.500.11940/16608
PMID: 32767480
ISSN: 2328-9503
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Date issued
2020
Journal title
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
Type of content
Journal Article
DeCS
complejo de endopeptidasas de los proteasomas | consanguinidad | adulto joven | síndrome | humanos | degeneraciones espinocerebelosas | proteínas F-box | epilepsia | adulto | paraplejía
MeSH
F-Box Proteins | Consanguinity | Adult | Humans | Epilepsy | Young Adult | Proteasome Endopeptidase Complex | Syndrome | Spinocerebellar Degenerations | Paraplegia
Abstract
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.
Atribución 4.0 Internacional
Except where otherwise noted, this item's license is described as Atribución 4.0 Internacional