ArticleNeurology. Genetics2016
Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia.
Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- The Differing Phenotypes of the Three Most Common Postsynaptic Congenital Myasthenic Syndromes Governed by Their Underlying Molecular Pathogenic Mechanisms.Muscle & nerve · 2026Review
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Novel Potential Risk Loci for Migraine in the Portuguese Population.International journal of molecular sciences · 2026Article
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.Nature genetics · 2025Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Loss of synaptic Munc13-1 underlies neurotransmission abnormalities in spinal muscular atrophy.Cellular and molecular life sciences : CMLS · 2025Article
- The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships.Genetics in medicine open · 2025Article
- Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2024Review
- Review
- Variants inJournal of medical genetics · 2023Article
- The era of cryptic exons: implications for ALS-FTD.Molecular neurodegeneration · 2023Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Genetic disorders of neurotransmitter release machinery.Frontiers in synaptic neuroscience · 2023Review
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Article
- The role of snare proteins in cortical development.Developmental neurobiology · 2022Review
- Similarity and Diversity of Presynaptic Molecules at Neuromuscular Junctions and Central Synapses.Biomolecules · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo identify the molecular basis of a fatal syndrome of microcephaly, cortical hyperexcitability, and myasthenia.
methodsWe performed clinical and in vitro microelectrode studies of neuromuscular transmission, examined neuromuscular junctions cytochemically and by electron microscopy (EM), and searched for mutations by Sanger and exome sequencing.
resultsNeuromuscular transmission was severely compromised by marked depletion of the readily releasable pool of quanta, but the probability of quantal release was normal. Cytochemical and EM studies revealed normal endplate architecture. Exome sequencing identified a homozygous nonsense mutation in the N-terminal domain of MUNC13-1 (UNC13A) truncating the protein after 101 residues.
conclusionsLoss of Munc13-1 function predicts that syntaxin 1B is consigned to a nonfunctional closed state; this inhibits cholinergic transmission at the neuromuscular junction and glutamatergic transmission in the brain. Inactivation of syntaxin 1B likely accounts for the patient's cortical hyperexcitability because mutations of syntaxin 1B cause febrile seizures with or without epilepsy, haploinsufficiency of the STX1B is associated with myoclonic astatic epilepsy, and antisense knockdown of stx1b in zebrafish larvae elicits epileptiform discharges. A very recent publication also shows that syntaxin 1B has a separate obligatory role for maintenance of developing and mature neurons and illustrates impaired brain development in syntaxin 1A/1B double knockout mice. We therefore attribute our patient's microcephaly to the truncating homozygous Munc13-1 mutation that consigns syntaxin 1B to a permanently closed nonfunctional state akin to a knockout.
Identifiers
What OpenQuestion 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 OpenQuestion graph.