ArticleEBioMedicine2024
Correlation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Increased Expression of α-Synuclein Impairs Trafficking of the Essential SNARE Protein Synaptobrevin-2.Journal of neurochemistry · 2026Article
- A novel de novo multi-exon deletion of SYT1 in a child with Baker-Gordon syndrome.BMC pediatrics · 2026Article
- Age-Related Characteristics of SYT1-Associated Neurodevelopmental Disorder.Annals of clinical and translational neurology · 2026Article
- Disease-causing mutations in Synaptotagmin can act via dominant-negative, gain-of-function or haploinsufficient mechanisms.bioRxiv : the preprint server for biology · 2026Article
- SP1 recruits TET1 to mediate Kif1a demethylation and synaptic remodeling in a mouse model of chronic migraine.The journal of headache and pain · 2026Article
- Regulation of spontaneous neurotransmission and homeostatic synaptic plasticity by synaptotagmin-1 disease variants at the SNARE primary interface.bioRxiv : the preprint server for biology · 2026Article
- Impaired Aggrephagy, Interrupted Vesicular Trafficking, and Cellular Stress, Lead to Protein Aggregation, and Synaptic Dysfunction in Cerebellum of Children and Adults with Idiopathic Autism.Cerebellum (London, England) · 2025Article
- Dimensionality reduction of quantitative EEG and clinical profiles uncover associations with monogenic neurodevelopmental phenotypes in SNAREopathies.Frontiers in neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPathogenic 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.
methodsHere, 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.
findingsWe show that recently identified variants within the facilitatory C2A domain of the protein (L159R, T196K, E209K, E219Q), as well as additional variants in the C2B domain (M303V, S309P, Y365C, G369D), share an underlying pathogenic mechanism, causing a graded and variant-dependent dominant-negative impairment in exocytosis. We establish that the extent of evoked exocytosis observed in vitro in the presence of SYT1 variants correlates with neurodevelopmental impacts of this disorder. Specifically, the severity of motor and communication impairments exhibited by individuals harbouring these variants correlates with multiple measures of exocytic efficiency.
interpretationTogether, this suggests that there is a genotype-function-phenotype relationship in SYT1-associated neurodevelopmental disorder, centring impaired evoked neurotransmitter release as a common pathogenic driver. Moreover, this points toward a direct link between control of neurotransmitter release and development of adaptive functions, providing a tractable target for therapeutic amelioration.
fundingAustralian National Health and Medical Research Council, UK Medical Research Council, Great Ormond Street Hospital Children's Charity, University of Melbourne.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.