Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect.
Ann Clin Transl Neurol
; 7(8): 1436-1442, 2020 08.
Article
in En
| MEDLINE
| ID: mdl-32767480
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neuroaxonal Dystrophies
/
Iron Metabolism Disorders
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Parkinsonian Disorders
/
F-Box Proteins
/
Proteasome Endopeptidase Complex
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
Language:
En
Journal:
Ann Clin Transl Neurol
Year:
2020
Type:
Article
Affiliation country:
Spain