Search results for "Synaptopathy"

showing 3 items of 3 documents

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

2019

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved resid…

MaleHeterozygoteAdolescentVesicle-Associated Membrane Protein 2neuronal exocytosisynaptopathyautismsynaptobrevinMembrane FusionExocytosisR-SNARE ProteinsProtein DomainsReportIntellectual DisabilityGeneticsHumansAutistic DisorderChildGenetics (clinical)NeuronsNeurotransmitter Agentsneurodevelopmental disordersvesicle fusionBrainautism; epilepsy; movement disorders; neurodevelopmental disorders; neuronal exocytosis; SNARE; synaptobrevin; synaptopathy; VAMP2; vesicle fusionneuronal exocytosisLipidsMagnetic Resonance Imagingneurodevelopmental disorderautism epilepsy movement disorders neurodevelopmental disorders neuronal exocytosis SNARE synaptobrevin synaptopathy VAMP2 vesicle fusion Genetics Genetics (clinical)Phenotypeautism; epilepsy; movement disorders; neurodevelopmental disorders; neuronal exocytosis; SNARE; synaptobrevin; synaptopathy; VAMP2; vesicle fusion; Genetics; Genetics (clinical)VAMP2SNAREChild PreschoolMutationSynapsesMuscle Hypotoniaepilepsymovement disordersFemalesense organsmovement disorder
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DLG4-related synaptopathy: a new rare brain disorder

2021

Contains fulltext : 245031.pdf (Publisher’s version ) (Closed access) PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyp…

0301 basic medicineAutism Spectrum Disorder[SDV]Life Sciences [q-bio]030105 genetics & heredityBiology03 medical and health sciencesIntellectual DisabilityIntellectual disabilitymedicineMissense mutationHumansGlobal developmental delayExomeGenetics (clinical)GeneticsBrain DiseasesNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]Brainmedicine.disease030104 developmental biologyPhenotypeRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]Autism spectrum disorderNeurodevelopmental DisordersSynaptopathyDLG4Postsynaptic densityDisks Large Homolog 4 Protein
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2019

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved resid…

0301 basic medicineVesicle fusionVAMP2SynaptobrevinSNAP25Biologymedicine.diseaseSynaptic vesicleExocytosisCell biology03 medical and health scienceschemistry.chemical_compound030104 developmental biology0302 clinical medicinechemistryGeneticsmedicineSynaptopathysense organsNeurotransmitter030217 neurology & neurosurgeryGenetics (clinical)The American Journal of Human Genetics
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