ArticleAnnals of clinical and translational neurology2017
Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome.
Article in Annals of clinical and translational neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases.Pediatric neurology · 2024Article
- Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals.Journal of human genetics · 2024Article
- 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
- Similarity and Diversity of Presynaptic Molecules at Neuromuscular Junctions and Central Synapses.Biomolecules · 2022Review
- [Advances in the diagnosis and treatment of congenital myasthenic syndrome].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- Membrane trafficking in health and disease.Disease models & mechanisms · 2020Review
- Quantitative Changes in the Mitochondrial Proteome of Cerebellar Synaptosomes From Preclinical Cystatin B-Deficient Mice.Frontiers in molecular neuroscience · 2020Article
- The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies.Current opinion in neurology · 2019Review
- Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment.American journal of human genetics · 2019Article
- [Congenital myasthenic syndromes in adulthood : Challenging, rare but treatable].Der Nervenarzt · 2019Review
- The Electrophysiology of Presynaptic Congenital Myasthenic Syndromes With and Without Facilitation: From Electrodiagnostic Findings to Molecular Mechanisms.Frontiers in neurology · 2019Review
- Fast and slow-twitching muscles are differentially affected by reduced cholinergic transmission in mice deficient for VAChT: A mouse model for congenital myasthenia.Neurochemistry international · 2018Article
- Congenital Myasthenic Syndromes: a Clinical and Treatment Approach.Current treatment options in neurology · 2018Review
- Congenital Myasthenic Syndromes in 2018.Current neurology and neuroscience reports · 2018Review
- How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features.Neuromolecular medicine · 2018Review
- Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A.Molecular genetics & genomic medicine · 2018Article
- The unfolding landscape of the congenital myasthenic syndromes.Annals of the New York Academy of Sciences · 2018Review
Corrections and comments
- Erratum issuedCorrigendum.2017
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveTo identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome.
methodsWe performed clinical electrophysiology studies, exome and Sanger sequencing, and analyzed functional consequences of the identified mutation.
resultsClinical electrophysiology studies of the patient revealed several-fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect. Exome sequencing identified a homozygous c.340delA frameshift mutation in synaptobrevin 1 (SYB1), one of the three SNARE proteins essential for synaptic vesicle exocytosis. Analysis of both human spinal cord gray matter and normal human muscle revealed expression of the SYB1A and SYB1D isoforms, predicting expression of one or both isoforms in the motor nerve terminal. The identified mutation elongates the intravesicular C-terminus of the A isoform from 5 to 71, and of the D isoform from 4 to 31 residues. Transfection of either mutant isoform into bovine chromaffin cells markedly reduces depolarization-evoked exocytosis, and transfection of either mutant isoform into HEK cells significantly decreases expression of either mutant compared to wild type.
interpretationThe mutation is pathogenic because elongation of the intravesicular C-terminus of the A and D isoforms increases the energy required to move their C-terminus into the synaptic vesicle membrane, a key step for fusion of the synaptic vesicle with the presynaptic membrane, and because it is predicted to reduce expression of either isoform in the nerve terminal.
Identifiers
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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.