ArticleBrain : a journal of neurology2020
Homozygous STXBP1 variant causes encephalopathy and gain-of-function in synaptic transmission.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Associations of Cortical and Subcortical White Matter Morphometric Abnormalities With Clinical and Genetic Findings inNeurology. Genetics · 2026Article
- STXBP1 Variants Associated With Epilepsy With Variable Severity.CNS neuroscience & therapeutics · 2026Article
- Phenotypic diversity is caused by non-linear genetic interactions between two SNAREopathy genes.Molecular psychiatry · 2026Article
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research.Biotech (Basel (Switzerland)) · 2025Review
- Developmental and Epileptic Encephalopathies: Need for Bridging the Gaps Between Clinical Syndromes and Underlying Genetic Etiologies.Indian journal of pediatrics · 2025Review
- Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse.Frontiers in neurology · 2025Article
- A de novo missense mutation in synaptotagmin-1 associated with neurodevelopmental disorder desynchronizes neurotransmitter release.Molecular psychiatry · 2024Article
- Reduced synaptic depression in human neurons carrying homozygous disease-causing STXBP1 variant L446F.Human molecular genetics · 2024Article
- Allelic heterogeneity and abnormal vesicle recycling inFrontiers in molecular neuroscience · 2024Article
- Reduced MUNC18-1 Levels, Synaptic Proteome Changes, and Altered Network Activity inBiological psychiatry global open science · 2024Article
- Review
- Delineating clinical and developmental outcomes in STXBP1-related disorders.Brain : a journal of neurology · 2023Article
- Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy.European journal of human genetics : EJHG · 2023Article
- Case report: A novelFrontiers in neurology · 2023Article
- Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in theFrontiers in molecular neuroscience · 2023Article
- Clinical variants inGenetics in medicine open · 2023Article
- Exploration and validation of m7G-related genes as signatures in the immune microenvironment and prognostic indicators in low-grade glioma.American journal of translational research · 2023Article
- Genetic disorders of neurotransmitter release machinery.Frontiers in synaptic neuroscience · 2023Review
- Complex spiking neural networks with synaptic time-delay based on anti-interference function.Cognitive neurodynamics · 2022Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterozygous mutations in the STXBP1 gene encoding the presynaptic protein MUNC18-1 cause STXBP1 encephalopathy, characterized by developmental delay, intellectual disability and epilepsy. Impaired mutant protein stability leading to reduced synaptic transmission is considered the main underlying pathogenetic mechanism. Here, we report the first two cases carrying a homozygous STXBP1 mutation, where their heterozygous siblings and mother are asymptomatic. Both cases were diagnosed with Lennox-Gastaut syndrome. In Munc18-1 null mouse neurons, protein stability of the disease variant (L446F) is less dramatically affected than previously observed for heterozygous disease mutants. Neurons expressing Munc18L446F showed minor changes in morphology and synapse density. However, patch clamp recordings demonstrated that L446F causes a 2-fold increase in evoked synaptic transmission. Conversely, paired pulse plasticity was reduced and recovery after stimulus trains also. Spontaneous release frequency and amplitude, the readily releasable vesicle pool and the kinetics of short-term plasticity were all normal. Hence, the homozygous L446F mutation causes a gain-of-function phenotype regarding release probability and synaptic transmission while having less impact on protein levels than previously reported (heterozygous) mutations. These data show that STXBP1 mutations produce divergent cellular effects, resulting in different clinical features, while sharing the overarching encephalopathic phenotype (developmental delay, intellectual disability and epilepsy).
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