Open AccessImpaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect
Author(s) -
CorreaVela Marta,
Lupo Vincenzo,
Montpeyó Marta,
Sancho Paula,
MarcéGrau Anna,
HernándezVara Jorge,
Darling Alejandra,
Jenkins Alison,
FernándezRodríguez Sandra,
Tello Cristina,
RamírezJiménez Laura,
Pérez Belén,
SánchezMontáñez Ángel,
Macaya Alfons,
Sobrido María J.,
MartinezVicente Marta,
PérezDueñas Belén,
Espinós Carmen
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51095
Subject(s) - neurodegeneration , parkinsonism , proteasome , medicine , parkin , ubiquitin , hereditary spastic paraplegia , microbiology and biotechnology , phenotype , parkinson's disease , pathology , disease , biology , biochemistry , gene
Abstact 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.