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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.
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The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11;
Myoclonus-dystonia syndrome is a childhood-onset movement disorder related to mutations in the SGCE gene. 1 The gene encodes εsarcoglycan, a transmembrane protein with a brain-specific isoform. This genetic defect has autosomal dominant transmission with reduced penetrance because of maternal imprinting. 2 The myoclonus phenotype of SGCE-myoclonusdystonia has been extensively assessed in previous studies, including our own paediatric cohort. [3][4][5] In these studies, myoclonus has been reported to be more severe than dystonia. However, the dystonic phenotype has been evaluated mostly with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), a scale designed for primary generalized dystonia. Because dystonia in patients with SGCEmyoclonus-dystonia is predominantly task specific and shows a segmental distribution, there could have been a
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