ArticleJournal of human genetics2018
Biallelic mutations in FDXR cause neurodegeneration associated with inflammation.
Article in Journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04580979 (A Natural History Study of Neurodegeneration and Optic Atrophy Caused by Ferredoxin Reductase Mutations in Pediatric and Adult Patients), which is not on this map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Natural History Study of Neurodegeneration and Optic Atrophy Caused by Ferredoxin Reductase Mutations in Pediatric and Adult Patients
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Genotype-Phenotype Relationships in Patients Carrying BiallelicHuman mutation · 2026Pooled it
- FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Pooled it
- Homozygous FDXR variant in twin sisters with spastic paraparesis followed by acute progressive flaccid quadriparesis.BMC neurology · 2026Article
- Article
- Ferroptosis is a novel pathogenic mechanism of FDXR-related disease via disruption of the NRF2 pathway.Cell death discovery · 2025Article
- A molecular basis of Ferredoxin Reductase (FdxR) mutations that result in mitochondriopathies.Journal of inorganic biochemistry · 2025Article
- Disordered Electron Transfer: New Forms of Defective Steroidogenesis and Mitochondriopathy.The Journal of clinical endocrinology and metabolism · 2025Review
- Identification of genetic mechanisms of non-isolated auditory neuropathy with various phenotypes in Chinese families.Orphanet journal of rare diseases · 2025Article
- Article
- Clinical study of ferredoxin-reductase-related mitochondriopathy: Genotype-phenotype correlation and proposal of ancestry-based carrier screening in the Mexican population.Genetics in medicine open · 2024Article
- Article
- History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology.Endocrine reviews · 2023Article
- Therapeutic Targeting of Ovarian Cancer Stem Cells Using Estrogen Receptor Beta Agonist.International journal of molecular sciences · 2022Article
- Diagnostic testing laboratories are valuable partners for disease gene discovery: 5-year experience with GeneMatcher.Human mutation · 2022Article
- Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management.Endocrine reviews · 2022Review
- Mechanisms of MEHP Inhibitory Action and Analysis of Potential Replacement Plasticizers on Leydig Cell Steroidogenesis.International journal of molecular sciences · 2021Article
- Steroidogenic electron-transfer factors and their diseases.Annals of pediatric endocrinology & metabolism · 2021Article
- Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.Investigative ophthalmology & visual science · 2021Article
- Novel biallelic compound heterozygous mutations in FDXR cause optic atrophy in a young female patient: a case report.International journal of ophthalmology · 2021Article
- Systemic Delivery of AAV-Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Mitochondrial dysfunction lies behind many neurodegenerative disorders, owing largely to the intense energy requirements of most neurons. Such mitochondrial dysfunction may work through a variety of mechanisms, from direct disruption of the electron transport chain to abnormal mitochondrial biogenesis. Recently, we have identified biallelic mutations in the mitochondrial flavoprotein "ferredoxin reductase" (FDXR) gene as a novel cause of mitochondriopathy, peripheral neuropathy, and optic atrophy. In this report, we expand upon those results by describing two new cases of disease-causing FDXR variants in patients with variable severity of phenotypes, including evidence of an inflammatory response in brain autopsy. To investigate the underlying pathogenesis, we examined neurodegeneration in a mouse model. We found that Fdxr mutant mouse brain tissues share pathological changes similar to those seen in patient autopsy material, including increased astrocytes. Furthermore, we show that these abnormalities are associated with increased levels of markers for both neurodegeneration and gliosis, with the latter implying inflammation as a major factor in the pathology of Fdxr mutations. These data provide further insight into the pathogenic mechanism of FDXR-mediated central neuropathy, and suggest an avenue for mechanistic studies that will ultimately inform treatment.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.