TY - JOUR
T1 - Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect
AU - Correa-Vela, Marta
AU - Lupo, Vincenzo
AU - Montpeyó Garcia-Moreno, Marta
AU - Sancho, Paula
AU - Marcé-Grau, Anna
AU - Hernández-Vara, Jorge
AU - Darling, Alejandra
AU - Jenkins, Alison
AU - Fernández-Rodríguez, Sandra
AU - Tello, Cristina
AU - Ramírez-Jiménez, Laura
AU - Pérez, Belén
AU - Sánchez-Montáñez, Ángel
AU - Macaya Ruiz, Alfons
AU - Sobrido, María J.
AU - Martinez-Vicente, Marta
AU - Pérez-Dueñas, Belén
AU - Espinós, Carmen
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85089028331
U2 - 10.1002/acn3.51095
DO - 10.1002/acn3.51095
M3 - Article
C2 - 32767480
SN - 2328-9503
VL - 7
SP - 1436
EP - 1442
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
ER -