biostudies-literatureUnknown109Park PY<h4>Background</h4>Pathogenic missense variants in the essential synaptic vesicle protein synaptotagmin-1 (SYT1) cause a neurodevelopmental disorder characterised by motor delay and intellectual disability, hyperkinetic movement disorder, episodic agitation, and visual impairments. SYT1 is the presynaptic calcium sensor that triggers synchronous neurotransmitter release. We have previously shown that pathogenic variants around the calcium-sensing region of the critical C2B domain decrease synaptic vesicle exocytosis in neurons.<h4>Methods</h4>Here, we have used cultured hippocampal neurons transfected with SYT1-pHluorin to examine how variants within the C2A and C2B domain of SYT1 impact evoked exocytosis.<h4>Findings</h4>We show that recently identified variants within the facilitatory C2EBioMedicine105416https://www.ebi.ac.uk/biostudies/studies/S-EPMC11564929biostudies-literatureCorrelation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.PMC11564929Baker KAl-Jawahiri RAloi MAMelland HSaraya NGordon SLEck JBleakley LEPark PYfalseCorrelation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.<h4>Background</h4>Pathogenic missense variants in the essential synaptic vesicle protein synaptotagmin-1 (SYT1) cause a neurodevelopmental disorder characterised by motor delay and intellectual disability, hyperkinetic movement disorder, episodic agitation, and visual impairments. SYT1 is the presynaptic calcium sensor that triggers synchronous neurotransmitter release. We have previously shown that pathogenic variants around the calcium-sensing region of the critical C2B domain decrease synaptic vesicle exocytosis in neurons.<h4>Methods</h4>Here, we have used cultured hippocampal neurons transfected with SYT1-pHluorin to examine how variants within the C2A and C2B domain of SYT1 impact evoked exocytosis.<h4>Findings</h4>We show that recently identified variants within the facilitatory C22024-01-01T00:00:00Z2024 Nov2026-06-01T07:18:28.928Z2025-04-06T22:46:19.989ZS-EPMC115649293948120910.1016/j.ebiom.2024.105416