ArticleAmerican journal of human genetics2016
Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Effectiveness of Riboflavin in Inherited Metabolic Diseases: A Systematic Review.Journal of inherited metabolic disease · 2026Pooled it
- A familial case of FLAD1 protein deficiency associated with impaired adrenal steroidogenesis.JCI insight · 2026Article
- Whole-Genome-Guided Functional Characterization ofFoods (Basel, Switzerland) · 2026Article
- Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.International journal of molecular sciences · 2026Review
- Spinal Cord Involvement in Patients with Adult-Onset Multiple Acyl-CoA Dehydrogenase Deficiency.Neuromolecular medicine · 2026Article
- Mitochondrial disease management through phytochemical interventions.Molecular and cellular biochemistry · 2025Review
- Glycerol mediates crosstalk between metabolism and trafficking through the golgin Imh1.Nature structural & molecular biology · 2025Article
- The FTO-YTHDF2 axis drives immune evasion and tumor progression in hepatocellular carcinoma via m6A-dependent FLAD1 regulation.Journal of molecular histology · 2025Article
- Copy number amplification of FLAD1 promotes the progression of triple-negative breast cancer through lipid metabolism.Nature communications · 2025Article
- Disorders of fatty acid homeostasis.Journal of inherited metabolic disease · 2025Review
- Integrative single-cell and spatial transcriptomics analysis reveals FLAD1 as a regulator of the immune microenvironment in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Comprehensive safety assessment of Qiwei Tiexie Pill: integrating histopathological, biochemical, and metabolomic analyses in a rat model.Frontiers in pharmacology · 2025Article
- Riboflavin in neurological diseases: therapeutic advances, metabolic insights, and emerging genetic strategies.Frontiers in neurology · 2025Review
- Fatal multiple acyl-CoA dehydrogenase deficiency caused byWorld journal of clinical cases · 2024Article
- Revitalising Riboflavin: Unveiling Its Timeless Significance in Human Physiology and Health.Foods (Basel, Switzerland) · 2024Review
- Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations.Molecular genetics and genomics : MGG · 2024Article
- A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene.Journal of human genetics · 2024Article
- Identification and functional prediction of lncRNAs associated with intramuscular lipid deposition in Guangling donkeys.Frontiers in veterinary science · 2024Article
- New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases.Nutrition & metabolism · 2023Review
- Detection ofAnnals of medicine and surgery (2012) · 2023Article
13 more citing papers are in PubMed but not listed here.
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48 authors at 20 institutions in 10 countries.
Funding
Abstract
Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis.
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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.