ArticleBrain : a journal of neurology2019
Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pooled it
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- Implications of mitochondrial phosphatidylethanolamine in neuronal health and neurodegeneration.Neural regeneration research · 2026Article
- Homeostatic response of phospholipid pathways to PCYT2 deficiency and impaired de Novo synthesis of phosphatidylethanolamine.Scientific reports · 2025Article
- Iron and selenium: At the crossroads of development and death in oligodendrocytes.Archives of biochemistry and biophysics · 2025Review
- Targeting phospholipase PLAG-15 promotes healthy aging iniScience · 2025Article
- Spastic Paraplegia 82 in Two Asian Indian Siblings With PCYT2 Mutations.Journal of movement disorders · 2025Article
- Glycerophospholipids: Roles in Cell Trafficking and Associated Inborn Errors.Journal of inherited metabolic disease · 2025Review
- Histone demethylase inhibitor KDM5-C70 regulates metabolomic and lipidomic programming during an astrocyte differentiation of rat neural stem cell.Scientific reports · 2025Article
- Biallelic PTPMT1 variants disrupt cardiolipin metabolism and lead to a neurodevelopmental syndrome.Brain : a journal of neurology · 2025Article
- Epigenome-wide methylation analysis shows phosphonoethylamine alleviates aberrant DNA methylation in NASH caused by Pcyt2 deficiency.PloS one · 2025Article
- PCYT2 overexpression induces mitochondrial damage and promotes apoptosis in hepatocellular carcinoma cells.PloS one · 2025Article
- PCYT2 inhibits epithelial-mesenchymal transition in colorectal cancer by elevating YAP1 phosphorylation.JCI insight · 2024Article
- Translatome analysis in acute ischemic stroke: Astrocytes and microglia exhibit differences in poststroke alternative splicing of expressed transcripts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Adding metabolic tasks to human GEM models to improve the study of gene targets and their associated toxicities.Scientific reports · 2024Article
- Dietary linoleic acid supplementation fails to rescue established cardiomyopathy in Barth syndrome.Journal of molecular and cellular cardiology plus · 2024Article
- A conserved complex lipid signature marks human muscle aging and responds to short-term exercise.Nature aging · 2024Article
- The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia.American journal of respiratory and critical care medicine · 2024Article
- Plasma Lipidomic Profiles in cART-Treated Adolescents with Perinatally Acquired HIV Compared to Matched Controls.Viruses · 2024Article
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
25 authors at 7 institutions in 5 countries.
Funding
Abstract
ctpphosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via the CDP-ethanolamine pathway. Phosphatidylethanolamine is one of the most abundant membrane lipids and is particularly enriched in the brain. We identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy. Using patient fibroblasts we demonstrated that these variants are hypomorphic, result in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR-Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. In conclusion, our data establish PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirm that etherlipid homeostasis is important for the development and function of the brain.
Indexed as
Identifiers
What Socratic 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 Socratic graph.