ArticleAmerican journal of human genetics2012
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.Scientific reports · 2016Pooled it
- CYP2U1: a cardiac metabolic switch alleviating obesity cardiomyopathy via lipid metabolic reprogramming.Molecular and cellular biochemistry · 2026Article
- APOE-stratified genome-wide association analyses provide insights into the genetic etiology of Alzheimers's disease.Nature genetics · 2026Article
- Hereditary neurodegenerative disorders with spastic-ataxic manifestations: genetic and clinical insights into previously reported variants.Neurogenetics · 2026Article
- Neurodevelopmental alterations are key drivers of SPG56.Human molecular genetics · 2026Article
- Early-onset hereditary spastic paraplegia type 56 (SPG56): clinical-molecular correlations and functional validation of CYP2U1 variants.BMC medical genomics · 2026Article
- Dystonia as an early and prominent feature in a patient with CYP2U1 gene mutation: expanding the phenotype of SPG56-a case report.Orphanet journal of rare diseases · 2026Article
- Genotypic and phenotypic spectrum of hereditary spastic paraplegia 56: insights from novel CYP2U1 variants and a literature review.BMC neurology · 2026Review
- Charting the genetic landscape of autosomal recessive hereditary spastic paraplegia: A deep dive into 10 exceptionally rare cases.Neurogenetics · 2025Article
- Advancing neurogenetics in Africa: past achievements, current developments and shaping the future.Nature reviews. Neurology · 2025Review
- Multiomics Approach Reveal Novel Insights in FUS Driven Juvenile Amyotrophic Lateral Sclerosis: A Family Quartet Analysis.Annals of neurosciences · 2025Article
- Glycerophospholipids: Roles in Cell Trafficking and Associated Inborn Errors.Journal of inherited metabolic disease · 2025Review
- Three Iranian patients with rare subtypes of hereditary spastic paraplegia (HSP): SPG76, SPG56, and SPG69.Neurogenetics · 2024Article
- Thalamic Deep Brain Stimulation for SPG56-Related Focal Hand Dystonia.Journal of movement disorders · 2024Article
- Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.PLoS genetics · 2024Article
- Cardiolipin remodeling maintains the inner mitochondrial membrane in cells with saturated lipidomes.Journal of lipid research · 2024Article
- Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity.Journal of xenobiotics · 2024Review
- CYP2U1: An emerging treatable neurometabolic disease with cerebral folate deficiency in 2 Chinese brothers.Molecular genetics and metabolism reports · 2024Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- Movement disorders in hereditary spastic paraplegias.Arquivos de neuro-psiquiatria · 2023Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 20 institutions in 8 countries.
Funding
Abstract
Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function.
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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.