A5002312741- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Ion channel regulation and function
- Genomics and Rare Diseases
- Receptor Mechanisms and Signaling
- Neurogenetic and Muscular Disorders Research
Emory University
2014-2024
Central South University
2017
Xiangya Hospital Central South University
2017
Objective Early-onset epileptic encephalopathies have been associated with de novo mutations of numerous ion channel genes. We employed techniques modern translational medicine to identify a disease-causing mutation, analyze its altered behavior, and screen for therapeutic compounds treat the proband. Methods Three tools were utilized: (1) high-throughput sequencing technology novel mutation; (2) in vitro expression electrophysiology assays confirm variant protein's dysfunction; (3)...
N-methyl-D-aspartate receptors (NMDARs), ligand-gated ionotropic glutamate receptors, play key roles in normal brain development and various neurological disorders. Here we use standing variation data from the human population to assess which protein domains within NMDAR GluN1, GluN2A GluN2B subunits show strongest signal for being depleted of missense variants. We find that this includes GluN2 pre-M1 helix linker between agonist-binding domain (ABD) first transmembrane (M1). then evaluate...
Abstract N-methyl- d -aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout central nervous system. Genetic variants GRIN genes encoding NMDAR subunits associated with a spectrum neurological disorders. The M3 transmembrane helices couple directly to agonist-binding domains form helical bundle crossing closed that occludes pore. functions as transduction element whose conformational change couples ligand...
The N-methyl-d-aspartate receptor (NMDAR), a ligand-gated ionotropic glutamate receptor, plays important roles in normal brain development and wide range of neurologic disorders, including epilepsy. Here, we evaluate for the first time functional properties de novo <i>GRIN2A</i> missense mutation (p.M817V) pre-M4 linker child with profound global developmental delay refractory Electrophysiologic recordings revealed that mutant GluN2A(M817V)-containing receptors showed enhanced agonist...
Objective N-methyl-D-aspartate receptors (NMDAR) subunit GRIN2A/GluN2A mutations have been identified in patients with various neurological diseases, such as epilepsy and intellectual disability / developmental delay (ID/DD). In this study, we investigated the phenotype underlying molecular mechanism of a GRIN2A missense mutation by next generation sequencing on idiopathic focal using vitro electrophysiology. Methods Genomic DNA ID/DD were sequenced targeted next-generation within 300 genes...