ArticleJIMD reports2016
Detailed Biochemical and Bioenergetic Characterization of FBXL4-Related Encephalomyopathic Mitochondrial DNA Depletion.
Article in JIMD reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- Activation of AMPK as a therapeutic strategy for FBXL4-related mitochondrial DNA depletion syndrome.EMBO molecular medicine · 2026Article
- Recessive PPTC7 deficiency triggers excessive mitophagy to cause a severe inborn error of metabolism with hypomyelinating leukodystrophy.Research square · 2026Article
- A Patient with Organic Acidemia, Hyperammonemia, and aMolecular syndromology · 2026Article
- Siblings of FBXL4-related mitochondrial DNA depletion syndrome, leading to fatal fulminant pneumonia.Molecular genetics and metabolism reports · 2025Article
- Dichloroacetate improves mitochondrial function, physiology, and morphology in FBXL4 disease models.JCI insight · 2022Article
- Dynamic features of human mitochondrial DNA maintenance and transcription.Frontiers in cell and developmental biology · 2022Review
- Review
- MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile.Frontiers in cellular neuroscience · 2021Article
- Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease.Frontiers in cardiovascular medicine · 2021Review
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes.Life (Basel, Switzerland) · 2020Review
- FBXL4 deficiency increases mitochondrial removal by autophagy.EMBO molecular medicine · 2020Article
- Thirty years of translational research in Mobility Medicine: Collection of abstracts of the 2020 Padua Muscle Days.European journal of translational myology · 2020Article
- Article
- Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome.Frontiers in genetics · 2019Article
- Hyperammonemia as a Presenting Feature in Two Siblings with FBXL4 Variants.JIMD reports · 2017Article
- Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency.JIMD reports · 2016Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of FBXL4, which encodes an orphan mitochondrial F-box protein, are a recently identified cause of encephalomyopathic mtDNA depletion. Here, we describe the detailed clinical and biochemical phenotype of a neonate presenting with hyperlactatemia, leukoencephalopathy, arrhythmias, pulmonary hypertension, dysmorphic features, and lymphopenia. Next-generation sequencing in the proband identified a homozygous frameshift, c.1641_1642delTG, in FBXL4, with a surrounding block of SNP marker homozygosity identified by microarray. Muscle biopsy showed a paucity of mitochondria with ultrastructural abnormalities, mitochondrial DNA depletion, and profound deficiency of all respiratory chain complexes. Cell-based mitochondrial phenotyping in fibroblasts showed mitochondrial fragmentation, decreased basal and maximal respiration, absence of ATP-linked respiratory and leak capacity, impaired survival under obligate aerobic respiration, and reduced mitochondrial inner membrane potential, with relative sparing of mitochondrial mass. Cultured fibroblasts from the patient exhibited a more oxidized glutathione ratio, consistent with altered cellular redox poise. High-resolution respirometry of permeabilized muscle fibers showed marked deficiency of oxidative phosphorylation using a variety of mitochondrial energy substrates and inhibitors. This constitutes the fourth and most detailed report of FBXL4 deficiency to date. In light of our patient's clinical findings and genotype (homozygous frameshift), this phenotype likely represents the severe end of the FBXL4 clinical spectrum.
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Registered trials
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