Related Experiment Video
Updated: Mar 7, 2026
07:11
Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity
Published on: September 19, 2025
1.2K
GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function
Wenjuan Chen1,2, Christine Shieh3, Sharon A Swanger1
1Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA.
Journal of Human Genetics
|February 24, 2017
Summary
Two individuals with de novo GRIN1 mutations experienced developmental delays and movement issues. These GRIN1 mutations alter N-methyl-d-aspartate receptor (NMDAR) function, impacting brain development and neurological disease.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- N-methyl-d-aspartate receptors (NMDARs) are crucial for brain development and are implicated in neurological disorders.
- Dominant de novo mutations in GRIN genes are increasingly recognized as causes of neurodevelopmental deficits.
Observation:
- Two individuals presented with similar symptoms including developmental delay, hypotonia, behavioral abnormalities, and stereotypical movements from birth.
- These individuals shared dominant de novo GRIN1 mutations (c.1858 G>A and c.1858 G>C), both resulting in the p.G620R amino acid change.
Findings:
- Recombinant NMDARs with the mutant GluN1-G620R subunit showed altered trafficking and electrophysiological properties.
- GluN1-G620R/GluN2A complexes exhibited reduced trafficking, decreased agonist potency, diminished Mg2+ block sensitivity, and lower maximal responses.
- GluN1-G620R/GluN2B complexes displayed significantly reduced surface delivery and similarly altered electrophysiology.
Implications:
- The observed deficits in NMDAR function and cell surface presence likely contribute to the neurodevelopmental issues in affected individuals.
- These findings highlight the critical role of NMDAR trafficking and function during embryonic brain development.
- Comprehensive functional characterization of de novo mutations is essential for understanding their impact on phenotype and neurological disease.
