ArticleEuropean journal of human genetics : EJHG2019
Novel calcineurin A (PPP3CA) variant associated with epilepsy, constitutive enzyme activation and downregulation of protein expression.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Epileptic-Dyskinetic Encephalopathy Associated with a PPP3CA Variant: Expansion of the Phenotypic Spectrum.Movement disorders clinical practice · 2026Article
- Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence.Biomolecules · 2026Article
- The clinical missense variant E282K in PPP3CA/calcineurin shifts substrate dephosphorylation by altering active site recruitment.Nature communications · 2026Article
- [Neuroprotective effects of idebenone combined with borneol via the dopamine signaling pathway in a transgenic zebrafish model of Parkinson's disease].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2025Article
- Remote spatial memory deficits in mouse models of neuropsychiatric disorders with immature dentate gyrus phenotype.The international journal of neuropsychopharmacology · 2025Article
- Engineered Extracellular Vesicles Loaded with MiR-100-5p Antagonist Selectively Target the Lesioned Region to Promote Recovery from Brain Damage.Neuroscience bulletin · 2025Article
- Regional and aging-specific cellular architecture of non-human primate brains.Genome medicine · 2025Article
- Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology.PloS one · 2025Article
- New variants and genotype-phenotype correlation ofFrontiers in neuroscience · 2025Article
- Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter.Orphanet journal of rare diseases · 2024Article
- Article
- Genomic evidence for the suitability of Göttingen Minipigs with a rare seizure phenotype as a model for human epilepsy.Neurogenetics · 2024Article
- A Study of Polish Family with Scoliosis and Limb Contractures Expands the MYH3 Disease Spectrum.Genes · 2024Article
- Population structure and selective signature of Kirghiz sheep by Illumina Ovine SNP50 BeadChip.PeerJ · 2024Article
- The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (International journal of molecular sciences · 2023Article
- The toxic natural product tutin causes epileptic seizures in mice by activating calcineurin.Signal transduction and targeted therapy · 2023Article
- Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice.Molecular brain · 2022Article
- Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort.Molecular cytogenetics · 2022Article
- Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-LinkedGenes · 2022Article
- Investigation of Copy Number Variations (CNVs) of the GoatAnimals : an open access journal from MDPI · 2022Article
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PPP3CA encodes calmodulin-binding catalytic subunit of calcineurin, a ubiquitously expressed calcium/calmodulin-regulated protein phosphatase. Recently de novo PPP3CA variants were reported as a cause of disease in 12 subjects presenting with epileptic encephalopathy and dysmorphic features. We describe a boy with similar phenotype and severe early onset epileptic encephalopathy in whom a novel de novo c.1324C>T (p.(Gln442Ter)) PPP3CA variant was found by whole exome sequencing. Western blot experiments in patient's cells (EBV transformed lymphocytes and neuronal cells derived through reprogramming) indicate that despite normal mRNA abundance the protein expression level is strongly reduced both for the mutated and wild-type protein. By in vitro studies with recombinant protein expressed in E. coli we show that c.1324C>T (p.(Gln442Ter)) results in constitutive activation of the enzyme. Our results confirm the role of PPP3CA defects in pathogenesis of a distinct neurodevelopmental disorder including severe epilepsy and dysmorphism and provide further functional clues regarding the pathogenic mechanism.
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Registered trials
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