Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect
Identificadores
Identificadores
URI: http://hdl.handle.net/20.500.11940/16837
PMID: 32767480
DOI: 10.1002/acn3.51095
ISSN: 2328-9503
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Fecha de publicación
2020Título de revista
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
Tipo de contenido
Journal Article
DeCS
complejo de endopeptidasas de los proteasomas | consanguinidad | adulto joven | síndrome | humanos | degeneraciones espinocerebelosas | proteínas F-box | epilepsia | adulto | paraplejíaMeSH
F-Box Proteins | Consanguinity | Adult | Humans | Epilepsy | Young Adult | Proteasome Endopeptidase Complex | Syndrome | Spinocerebellar Degenerations | ParaplegiaResumen
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.