ArticleThe Journal of clinical investigation2015
Identification of a human synaptotagmin-1 mutation that perturbs synaptic vesicle cycling.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review.The European journal of neuroscience · 2022Pooled it
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- 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
- Article
- Disease-causing mutations in Synaptotagmin can act via dominant-negative, gain-of-function or haploinsufficient mechanisms.bioRxiv : the preprint server for biology · 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
- Convergence and divergence of genes informed by common and rare variants of autism spectrum disorders in tissue-specific pathways and gene networks.Translational psychiatry · 2026Article
- Baker-Gordon Syndrome-Associated Synaptotagmin-1 Mutations Reduce Synaptic Strength in Mouse Primary and Human-Induced Neuronal Culture Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- Dimensionality reduction of quantitative EEG and clinical profiles uncover associations with monogenic neurodevelopmental phenotypes in SNAREopathies.Frontiers in neuroscience · 2025Article
- Exploring the Landscape of Pre- and Post-Synaptic Pediatric Disorders with Epilepsy: A Narrative Review on Molecular Mechanisms Involved.International journal of molecular sciences · 2024Review
- Correlation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.EBioMedicine · 2024Article
- Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization.The Journal of cell biology · 2024Article
- Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment.Current issues in molecular biology · 2024Review
- Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.Brain : a journal of neurology · 2024Article
- A de novo missense mutation in synaptotagmin-1 associated with neurodevelopmental disorder desynchronizes neurotransmitter release.Molecular psychiatry · 2024Article
- Lethal variant in the C2A domain may cause severe SYT1-associated neurodevelopmental disorder in the newborns.Neurogenetics · 2024Article
- c.1103T>C (p.Ile368Th) de novo Variant in Synaptotagmin 1 (International medical case reports journal · 2024Article
- Expanding the genetic and phenotypic spectrum of Baker-Gordon syndrome: a newJournal of genetics · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptotagmin-1 (SYT1) is a calcium-binding synaptic vesicle protein that is required for both exocytosis and endocytosis. Here, we describe a human condition associated with a rare variant in SYT1. The individual harboring this variant presented with an early onset dyskinetic movement disorder, severe motor delay, and profound cognitive impairment. Structural MRI was normal, but EEG showed extensive neurophysiological disturbances that included the unusual features of low-frequency oscillatory bursts and enhanced paired-pulse depression of visual evoked potentials. Trio analysis of whole-exome sequence identified a de novo SYT1 missense variant (I368T). Expression of rat SYT1 containing the equivalent human variant in WT mouse primary hippocampal cultures revealed that the mutant form of SYT1 correctly localizes to nerve terminals and is expressed at levels that are approximately equal to levels of endogenous WT protein. The presence of the mutant SYT1 slowed synaptic vesicle fusion kinetics, a finding that agrees with the previously demonstrated role for I368 in calcium-dependent membrane penetration. Expression of the I368T variant also altered the kinetics of synaptic vesicle endocytosis. Together, the clinical features, electrophysiological phenotype, and in vitro neuronal phenotype associated with this dominant negative SYT1 mutation highlight presynaptic mechanisms that mediate human motor control and cognitive development.
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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.