ArticleAmerican journal of human genetics2019
Mutations in PIGU Impair the Function of the GPI Transamidase Complex, Causing Severe Intellectual Disability, Epilepsy, and Brain Anomalies.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review.Frontiers in neurology · 2021Pooled it
- Shared molecular pathways in pediatric genetic epilepsies: Insights from a single-center cohort of 80 patients.Epilepsia open · 2026Article
- Neurodevelopmental Disorder with Dystonia and Chorea Linked to De Novo Variants in the Splicing Regulator SRRM4.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Radiation-Enhanced CD24 Membrane Trafficking via GPI Anchoring Mediates Antitumor Immune Evasion.Cancer research · 2026Article
- Role of Glycerophospholipid Metabolism in Epilepsy.Current neuropharmacology · 2026Review
- Molecular Insights into Fungal Glycosylphosphatidylinositol Transamidase Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biosynthesis of GPI anchored proteins, its deficiencies and treatment.Journal of human genetics · 2025Review
- Gut Microbiota and White Matter Integrity: A Two-Sample Mendelian Randomization Analysis.eNeuro · 2025Article
- Article
- Two novel cases with PIGQ-CDG: expansion of the genotype-phenotype spectrum and evaluation of GestaltMatcher as a diagnostic tool.Frontiers in genetics · 2025Article
- NRN1 may Modulate Tau Phosphorylation and Neuronal Apoptosis in ADCurrent Alzheimer research · 2025Article
- PIGK defects induce apoptosis in Purkinje cells and acceleration of neuroectodermal differentiation.Cell death & disease · 2024Article
- A novel homozygous variant of the PIGK gene caused by paternal disomy in a patient with neurodevelopmental disorder, cerebellar atrophy, and seizures.Journal of human genetics · 2024Article
- The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.Brain : a journal of neurology · 2024Observational
- Inherited glycosylphosphatidylinositol deficiency: a review from molecular and clinical perspectives.Acta biochimica et biophysica Sinica · 2024Review
- Article
- Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis.Nature communications · 2024Article
- Integrated analysis strategy of genome-wide functional gene mining reveals DKK2 gene underlying meat quality in Shaziling synthesized pigs.BMC genomics · 2024Article
- Macrocephaly and Digital Anomalies Expand the Phenotypic Spectrum ofHuman mutation · 2024Article
- Structure and Function of the Glycosylphosphatidylinositol Transamidase, a Transmembrane Complex Catalyzing GPI Anchoring of Proteins.Sub-cellular biochemistry · 2024Review
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glycosylphosphatidylinositol (GPI) anchor links over 150 proteins to the cell surface and is present on every cell type. Many of these proteins play crucial roles in neuronal development and function. Mutations in 18 of the 29 genes implicated in the biosynthesis of the GPI anchor have been identified as the cause of GPI biosynthesis deficiencies (GPIBDs) in humans. GPIBDs are associated with intellectual disability and seizures as their cardinal features. An essential component of the GPI transamidase complex is PIGU, along with PIGK, PIGS, PIGT, and GPAA1, all of which link GPI-anchored proteins (GPI-APs) onto the GPI anchor in the endoplasmic reticulum (ER). Here, we report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in five individuals from three unrelated families. All individuals presented with global developmental delay, severe-to-profound intellectual disability, muscular hypotonia, seizures, brain anomalies, scoliosis, and mild facial dysmorphism. Using multicolor flow cytometry, we determined a characteristic profile for GPI transamidase deficiency. On granulocytes this profile consisted of reduced cell-surface expression of fluorescein-labeled proaerolysin (FLAER), CD16, and CD24, but not of CD55 and CD59; additionally, B cells showed an increased expression of free GPI anchors determined by T5 antibody. Moreover, computer-assisted facial analysis of different GPIBDs revealed a characteristic facial gestalt shared among individuals with mutations in PIGU and GPAA1. Our findings improve our understanding of the role of the GPI transamidase complex in the development of nervous and skeletal systems and expand the clinical spectrum of disorders belonging to the group of inherited GPI-anchor deficiencies.
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