ArticleMovement disorders : official journal of the Movement Disorder Society2018
A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder.
Article in Movement disorders : official journal of the Movement Disorder Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 33 citations in OpenAlex.
- Neurodevelopmental disorder due to a frameshift mutation in theTranslational pediatrics · 2025Article
- Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options.Life (Basel, Switzerland) · 2025Review
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- An Unusual Case of GRIN2A Mutation Presenting as Progressive Limbic Encephalopathy in an Adult.Cureus · 2024Article
- Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.Physiological research · 2024Review
- De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Complex functional phenotypes of NMDA receptor disease variants.Molecular psychiatry · 2022Article
- ZniScience · 2022Article
- Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory.Molecular psychiatry · 2022Article
- Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing.Scientific reports · 2022Article
- Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners.International journal of molecular sciences · 2022Review
- Quantification of Behavioral Deficits in Developing Mice With Dystonic Behaviors.Dystonia (Lausanne, Switzerland) · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Article
- Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021Review
- Positive allosteric modulators that target NMDA receptors rectify loss-of-function GRIN variants associated with neurological and neuropsychiatric disorders.Neuropharmacology · 2020Article
- Hodgkin-Huxley-Katz Prize Lecture: Genetic and pharmacological control of glutamate receptor channel through a highly conserved gating motif.The Journal of physiology · 2020Article
- Cadmium activates AMPA and NMDA receptors with M3 helix cysteine substitutions.The Journal of general physiology · 2020Article
- GRIN2A: involvement in movement disorders and intellectual disability without seizures.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Article
- Cadmium opens GluK2 kainate receptors with cysteine substitutions at the M3 helix bundle crossing.The Journal of general physiology · 2019Article
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundMutations in the GRIN2A gene, which encodes the GluN2A (glutamate [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor, have been identified in patients with epilepsy-aphasia spectrum disorders, idiopathic focal epilepsies with centrotemporal spikes, and epileptic encephalopathies with severe developmental delay. However, thus far, mutations in this gene have not been associated with a nonepileptic neurodevelopmental disorder with dystonia.
objectivesThe objective of this study was to identify the disease-causing gene in 2 siblings with neurodevelopmental and movement disorders with no epileptiform abnormalities.
methodsThe study method was targeted next-generation sequencing panel for neuropediatric disorders and subsequent electrophysiological studies.
resultsThe 2 siblings carry a novel missense mutation in the GRIN2A gene (p.Ala643Asp) that was not detected in genomic DNA isolated from blood cells of their parents, suggesting that the mutation is the consequence of germinal mosaicism in 1 progenitor. In functional studies, the GluN2A-A643D mutation increased the potency of the agonists L-glutamate and glycine and decreased the potency of endogenous negative modulators, including protons, magnesium and zinc but reduced agonist-evoked peak current response in mammalian cells, suggesting that this mutation has a mixed effect on N-methyl-d-aspartate receptor function.
conclusionDe novo GRIN2A mutations can give rise to a neurodevelopmental and movement disorder without epilepsy. © 2018 International Parkinson and Movement Disorder Society.
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