ArticleHuman molecular genetics2017
Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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 35 papers, 1 of them a synthesis 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- 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
- Neuroimaging in FDXR-related mitochondriopathy.Pediatric radiology · 2026Article
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Nuclear translocation of mitochondrial ferredoxin reductase is regulated by AKT-mediated phosphorylation.The Biochemical journal · 2026Article
- An intronic variant in Ferredoxin Reductase (FDXR) creates a cryptic exon in Quarter Horses with Equine Juvenile Spinocerebellar Ataxia.PLoS genetics · 2026Article
- Norepinephrine triggers ovarian granulosa cell ferroptosis via αJournal of ovarian research · 2026Article
- HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing ferroptosis in pregranulosa cells.Cellular and molecular life sciences : CMLS · 2026Article
- 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
- Hepatic ferredoxin reductase modulates mitochondrial function and iron homeostasis in metabolic dysfunction-associated steatotic liver disease.Research square · 2025Article
- Thirty years of StAR gazing. Expanding the universe of the steroidogenic acute regulatory protein.The Journal of endocrinology · 2025Review
- 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
- Identification of a distinct cluster of GDF15Frontiers in immunology · 2024Article
- Article
- History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology.Endocrine reviews · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
42 authors at 15 institutions in 4 countries.
Funding
Abstract
Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, including mitochondrial respiration, DNA repair, and iron homeostasis. A steadily increasing number of disorders are being associated with disrupted biogenesis of Fe-S clusters. Here, we conducted whole-exome sequencing of patients with optic atrophy and other neurological signs of mitochondriopathy and identified 17 individuals from 13 unrelated families with recessive mutations in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin reductase required for electron transport from NADPH to cytochrome P450. In vitro enzymatic assays in patient fibroblast cells showed deficient ferredoxin NADP reductase activity and mitochondrial dysfunction evidenced by low oxygen consumption rates (OCRs), complex activities, ATP production and increased reactive oxygen species (ROS). Such defects were rescued by overexpression of wild-type FDXR. Moreover, we found that mice carrying a spontaneous mutation allelic to the most common mutation found in patients displayed progressive gait abnormalities and vision loss, in addition to biochemical defects consistent with the major clinical features of the disease. Taken together, these data provide the first demonstration that germline, hypomorphic mutations in FDXR cause a novel mitochondriopathy and optic atrophy in humans.
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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.