ArticleBrain : a journal of neurology2019
Heterogeneous clinical and functional features of GRIN2D-related developmental and epileptic encephalopathy.
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 52 papers.
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Who cites it
52 citing papers in PubMed, 88 citations in OpenAlex.
- GluN2D NMDA Receptors: Bridging Physiology and Pathology.Biological psychiatry · 2026Review
- GRIN-related epilepsy in Chinese pediatric patients: a retrospective study of clinical, genetic, and mutant protein structural features in a tertiary center cohort.World journal of pediatrics : WJP · 2026Article
- Single-nucleus profiling reveals a core disease signature and cell type-specific vulnerabilities in early Rett syndrome.Science advances · 2026Article
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- Inhibition of GluN2B-containing N-methyl-D-aspartate receptors by radiprodil.Brain : a journal of neurology · 2026Article
- Promotion of lung cancer growth via glutamate ionotropic receptor N-methyl-D-aspartate-type subunit 2D (Journal of thoracic disease · 2026Article
- A mouse model of GRIN2D developmental and epileptic encephalopathy recapitulates the human disease.Brain : a journal of neurology · 2026Article
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Synaptic dysregulation in a mouse model of GRIN2D developmental and epileptic encephalopathy.Brain : a journal of neurology · 2025Article
- Synchronized Hypsarrhythmia as a Potential EEG Signature in Genetic Infantile Epileptic Spasms Syndrome: Is there a Gene Network Association?Indian journal of pediatrics · 2025Article
- GRIN2B-related neurodevelopmental disorders: genotype-phenotype correlations and therapeutic implications.Orphanet journal of rare diseases · 2025Article
- Precision therapies for genetic epilepsies in 2025: Promises and pitfalls.Epilepsia open · 2025Article
- Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders.NPJ genomic medicine · 2025Article
- Ligand distances as key predictors of pathogenicity and function in NMDA receptors.Human molecular genetics · 2025Article
- Glutamate enhances the production of inflammatory cytokines IL-6 and IL-11, as well as chemokines CXCL2, CXCL3, and CXCL8 in keloid fibroblasts.Frontiers in molecular biosciences · 2025Article
- Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment.Current issues in molecular biology · 2024Review
- Chromosomal R-loops: who R they?Biologia futura · 2024Review
- Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.Human molecular genetics · 2024Article
- A Frameshift Variant of GluN2A Identified in an Epilepsy Patient Results in NMDA Receptor Mistargeting.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy.Methods in molecular biology (Clifton, N.J.) · 2024Review
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Authors and funding
28 authors at 13 institutions in 6 countries.
Funding
Abstract
N-methyl d-aspartate receptors are ligand-gated ionotropic receptors mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants in genes encoding NMDAR subunits have been associated with a spectrum of neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated GRIN2D variant in two patients with developmental and epileptic encephalopathy. GRIN2D encodes for the GluN2D subunit protein; the GluN2D amino acids affected by the variants in this report are located in the pre-M1 helix, transmembrane domain M3, and the intracellular carboxyl terminal domain. Functional analysis in vitro reveals that all six variants decreased receptor surface expression, which may underline some shared clinical symptoms. In addition the GluN2D(Leu670Phe), (Ala675Thr) and (Ala678Asp) substitutions confer significantly enhanced agonist potency, and/or increased channel open probability, while the GluN2D(Ser573Phe), (Ser1271Phe) and (Arg1313Trp) substitutions result in a mild increase of agonist potency, reduced sensitivity to endogenous protons, and decreased channel open probability. The GluN2D(Ser573Phe), (Ala675Thr), and (Ala678Asp) substitutions significantly decrease current amplitude, consistent with reduced surface expression. The GluN2D(Leu670Phe) variant slows current response deactivation time course and increased charge transfer. GluN2D(Ala678Asp) transfection significantly decreased cell viability of rat cultured cortical neurons. In addition, we evaluated a set of FDA-approved NMDAR channel blockers to rescue functional changes of mutant receptors. This work suggests the complexity of the pathological mechanisms of GRIN2D-mediated developmental and epileptic encephalopathy, as well as the potential benefit of precision medicine.
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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.