ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 122 citations in OpenAlex.
- New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.The Journal of biological chemistry · 2013Trial
- A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.The Journal of biological chemistry · 2012Trial
- Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.The Journal of biological chemistry · 2012Trial
- Purpose-Adaptable Reinforced 3D Hyaluronic-Acid Based Platform to Study Pathomechanisms of the Central Nervous System.Advanced healthcare materials · 2026Article
- Dynamics and Interplay of the Binding Pockets in the Glycine Receptor.Journal of chemical information and modeling · 2025Article
- A novel GLRB mutation in neonatal hyperekplexia with divergent EEG findings: a case series.Annals of medicine and surgery (2012) · 2025Article
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- In vitro human ion channel assays predictive of drug-induced seizure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- The emerging role of glycine receptor α2 subunit defects in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2025Review
- Exploring the Activation Process of the Glycine Receptor.Journal of the American Chemical Society · 2024Article
- Schisandrin B, a dual positive allosteric modulator of GABAActa pharmacologica Sinica · 2024Article
- Role of the Glycine Receptor β Subunit in Synaptic Localization and Pathogenicity in Severe Startle Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- An Adult Case of Genetically Confirmed Hyperekplexia Presenting with Head Trauma.NMC case report journal · 2024Article
- Liquid-liquid phase separation in synaptopathies.Neuroprotection (Chichester, England) · 2023Review
- Assaying Proliferation Characteristics of Cells Cultured Under Static Versus Periodic Conditions.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Inductive Stimuli of the Startle Response and Critical Points of Psychological Treatment in a Severe Burn Patient.Journal of burn care & research : official publication of the American Burn Association · 2022Article
- A NanoBiT assay to monitor membrane proteins trafficking for drug discovery and drug development.Communications biology · 2022Article
- Exploring the Conformational Impact of Glycine Receptor TM1-2 Mutations Through Coarse-Grained Analysis and Atomistic Simulations.Frontiers in molecular biosciences · 2022Article
- Loss, Gain and Altered Function of GlyR α2 Subunit Mutations in Neurodevelopmental Disorders.Frontiers in molecular neuroscience · 2022Article
- Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 13 institutions in 8 countries.
Funding
Abstract
Hyperekplexia is a rare, but potentially fatal, neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli. This disorder is primarily caused by inherited mutations in the genes encoding the glycine receptor (GlyR) alpha1 subunit (GLRA1) and the presynaptic glycine transporter GlyT2 (SLC6A5). In this study, systematic DNA sequencing of GLRA1 in 88 new unrelated human hyperekplexia patients revealed 19 sequence variants in 30 index cases, of which 21 cases were inherited in recessive or compound heterozygote modes. This indicates that recessive hyperekplexia is far more prevalent than previous estimates. From the 19 GLRA1 sequence variants, we have investigated the functional effects of 11 novel and 2 recurrent mutations. The expression levels and functional properties of these hyperekplexia mutants were analyzed using a high-content imaging system and patch-clamp electrophysiology. When expressed in HEK293 cells, either as homomeric alpha1 or heteromeric alpha1beta GlyRs, subcellular localization defects were the major mechanism underlying recessive mutations. However, mutants without trafficking defects typically showed alterations in the glycine sensitivity suggestive of disrupted receptor function. This study also reports the first hyperekplexia mutation associated with a GlyR leak conductance, suggesting tonic channel opening as a new mechanism in neuronal ligand-gated ion channels.
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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.