ArticleMolecular genetics and metabolism2016
Functional cellular analyses reveal energy metabolism defect and mitochondrial DNA depletion in a case of mitochondrial aconitase deficiency.
Article in Molecular genetics and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- SUCLG1 mutations and mitochondrial encephalomyopathy: a case study and review of the literature.Molecular biology reports · 2020Pooled it
- Development of a Novel Mitochondrial Dysfunction-Related Alzheimer's Disease Diagnostic Model Using Bioinformatics and Machine Learning.Current Alzheimer research · 2025Article
- Binding of α-synuclein to ACO2 promotes progressive mitochondrial dysfunction in Parkinson's disease models.Redox biology · 2024Article
- Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Whole exome sequencing in energy deficiency inborn errors of metabolism: A systematic review.Molecular genetics and metabolism reports · 2024Review
- Anaplerotic Therapy Using Triheptanoin in Two Brothers Suffering from Aconitase 2 Deficiency.Metabolites · 2024Article
- Biochemical characterization on muscle tissue of a novel biallelicJIMD reports · 2024Article
- Transcriptome analyses reveal molecular mechanisms of novel compound heterozygousFrontiers in cellular neuroscience · 2024Article
- ACO2 deficiency increases vulnerability to Parkinson's disease via dysregulating mitochondrial function and histone acetylation-mediated transcription of autophagy genes.Communications biology · 2023Article
- Child Neurology: Progressive Cerebellar Atrophy and Retinal Dystrophy: Clues to an UltrarareNeurology · 2023Article
- Superoxide Anion Chemistry-Its Role at the Core of the Innate Immunity.International journal of molecular sciences · 2023Review
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants inFrontiers in genetics · 2022Article
- An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases.Biomolecules · 2021Review
- Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism.Cell reports · 2021Article
- ACO2 clinicobiological dataset with extensive phenotype ontology annotation.Scientific data · 2021Article
- Molecular Mechanisms behind Inherited Neurodegeneration of the Optic Nerve.Biomolecules · 2021Review
- Complex hereditary spastic paraplegia associated with episodic visual loss caused by ACO2 variants.Human genome variation · 2021Article
- DominantBrain communications · 2021Article
- Haploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Defects in the tricarboxylic acid cycle (TCA) are associated with a spectrum of neurological phenotypes that are often difficult to diagnose and manage. Whole-exome sequencing (WES) led to a rapid expansion of diagnostic capabilities in such disorders and facilitated a better understanding of disease pathogenesis, although functional characterization remains a bottleneck to the interpretation of potential pathological variants. We report a 2-year-old boy of Afro-Caribbean ancestry, who presented with neuromuscular symptoms without significant abnormalities on routine diagnostic evaluation. WES revealed compound heterozygous missense variants of uncertain significance in mitochondrial aconitase (ACO2), which encodes the TCA enzyme ACO2. Pathogenic variants in ACO2 have been described in a handful of families as the cause of infantile cerebellar-retinal degeneration syndrome. Using biochemical and cellular assays in patient fibroblasts, we found that ACO2 expression was quantitatively normal, but ACO2 enzyme activity was <20% of that observed in control cells. We also observed a deficiency in cellular respiration and, for the first time, demonstrate evidence of mitochondrial DNA depletion and altered expression of some TCA components and electron transport chain subunits. The observed cellular defects were completely restored with ACO2 gene rescue. Our findings demonstrate the pathogenicity of two VUS in ACO2, provide novel mechanistic insights to TCA disturbances in ACO2 deficiency, and implicate mitochondrial DNA depletion in the pathogenesis of this recently described disorder.
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Registered trials
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