Annals of clinical and translational neurology · 2020
Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Correa-Vela Marta, Lupo Vincenzo, Montpeyó Marta, Sancho Paula, Marcé-Grau Anna, Hernández-Vara Jorge, Darling Alejandra, Jenkins Alison, Fernández-Rodríguez Sandra, Tello Cristina, Ramírez-Jiménez Laura, Pérez Belén, Sánchez-Montáñez Ángel, Macaya Alfons, Sobrido María J, Martinez-Vicente Marta, Pérez-Dueñas Belén, Espinós Carmen
Аннотация
UNLABELLED: 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.
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.