ArticleBrain : a journal of neurology2021
Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 47 citations in OpenAlex.
- From lipid dynamics to precision predictions: A new approach methodology for precision modeling of phosphoinositide signaling.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- E-Syt1 recruits PI4KA to endoplasmic reticulum-plasma membrane junctions to enhance PI4P synthesis.Science China. Life sciences · 2026Article
- Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity.The Journal of cell biology · 2026Article
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- Consensus-based detection of aetiologic copy number variants for syndromic orofacial clefts utilising whole exome sequencing of case parent trios.BMC genomic data · 2026Article
- Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.Cells · 2026Article
- Integrated environmental and genomic analysis reveals the drivers and genetic mechanisms of agro-climatic adaptation in geese.BMC genomics · 2026Article
- Pi4ka downregulation triggers Creb3l2-dependent lysosomal dysfunction to promote maladaptive tubular remodeling and immune activation in acute kidney injury.Cell death & disease · 2026Article
- Nitric oxide inhibition ameliorates cortical proteomic changes in the Cntnap2Molecular autism · 2026Article
- Consensus-based Detection of Aetiologic Copy Number Variants For Syndromic Orofacial Clefts Utilising Whole Exome Sequencing of Case Parent Trios.Research square · 2026Article
- Bi-allelic variants in the ribosomal protein RPS6KC1 cause a complex neurodevelopmental disorder.American journal of human genetics · 2025Article
- Neurogenetic Disorders with Hearing Loss: Mechanisms, Classifications, and Emerging Insights.Current neurology and neuroscience reports · 2025Review
- Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane.bioRxiv : the preprint server for biology · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Neurodevelopmental Disorder with Spasticity, Hypomyelinating Leukodystrophy, and Brain Abnormalities (NEDSPLB) in an Indian Child.Indian journal of pediatrics · 2025Article
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- An exploratory fetal MRI study examining the impact of 22q11.2 microdeletion syndrome on early brain growth.Journal of neurodevelopmental disorders · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Identifying novel heterozygous PI4KA variants in fetal abnormalities.BMC medical genomics · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
Corrections and comments
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Authors and funding
35 authors at 18 institutions in 4 countries.
Funding
Abstract
Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath.
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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.