ArticleMovement disorders : official journal of the Movement Disorder Society2020
The GRIA3 c.2477G > A Variant Causes an Exaggerated Startle Reflex, Chorea, and Multifocal Myoclonus.
Article in Movement disorders : official journal of the Movement Disorder Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Non-Convulsive Status Epilepticus and Mild Neurodevelopmental Phenotype in a Female with a Novel p.Thr657Ala Variant in theChildren (Basel, Switzerland) · 2025Article
- Evaluation, Diagnosis, and Treatment of Concomitant Movement Disorders in Genetic Epilepsies.Epilepsy currents · 2025Review
- Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment.Current issues in molecular biology · 2024Review
- Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.Brain : a journal of neurology · 2024Article
- Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes.Nature reviews. Neurology · 2024Review
- Clinical and functional consequences of GRIA variants in patients with neurological diseases.Cellular and molecular life sciences : CMLS · 2023Article
- Sleep Disorders in Patients with Choreic Syndromes.Current neurology and neuroscience reports · 2023Review
- GRIA3 p.Met661Thr variant in a female with developmental epileptic encephalopathy.Human genome variation · 2023Article
- Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human.Molecular psychiatry · 2022Article
- Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene.Neurogenetics · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3.PLoS genetics · 2021Article
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundHemizygous mutations in GRIA3 encoding the GluA3 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are known to be associated with neurodevelopmental disorders, including intellectual disability, hypotonia, an autism spectrum disorder, sleep disturbances, and epilepsy in males.
objectiveTo describe a new and consistent phenotype in 4 affected male patients associated with an undescribed deleterious variant in GRIA3.
methodsWe evaluated a large French family in which segregate a singular phenotype according to an apparent X-linked mode of inheritance. Molecular analyses using next generation sequencing and in vitro functional studies using 2-electrode voltage clamp recordings on Xenopus laevis oocytes and a β-lactamase reporter assay in transfected human embryonic kidney (HEK293) cells were performed.
resultsIn addition to mild intellectual disability and dysarthria, affected patients presented a tightly consistent early-onset movement disorder combining an exaggerated startle reflex with generalized chorea and multifocal myoclonus. The unreported GRIA3 missense variant c.2477G > A; p.(Gly826Asp) affecting the fourth transmembrane domain of the protein was identified in index patients and their unaffected mothers. Functional studies revealed that variant receptors show decreased current response evoked by agonist (ie, kainic acid and glutamate) and reduced expression on the cell surface in favor of pathogenicity by a loss-of-function mechanism.
conclusionsTaken together, our results suggest that apart from known GRIA3-related disorders, an undescribed mutation-specific singular movement disorder does exist. We thus advocate considering GRIA3 mutations in the differential diagnosis of hyperekplexia and generalized chorea with myoclonus. © 2020 International Parkinson and Movement Disorder Society.
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