ArticleAmerican journal of human genetics2009
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.
Article in American journal of human genetics, 2009. 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 93 papers, 2 of them syntheses 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
93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Ephedrine for myasthenia gravis, neonatal myasthenia and the congenital myasthenic syndromes.The Cochrane database of systematic reviews · 2014Pooled it
- Trial
- AGRN-, LRP4-, MUSK-Related CMS: Clinical, Neurophysiological, Morphological, Genetic and Pathological Mechanisms.Muscle & nerve · 2026Review
- The hallmarks of skeletal muscle health.Nature metabolism · 2026Review
- Distal Agrin (AGRN) Congenital Myasthenic Syndrome With Mitochondrial Dysfunction.European journal of neurology · 2026Article
- Gene-specific response to muscle specific kinase agonist antibody in the treatment of congenital myasthenic syndromes.Brain communications · 2026Article
- Proteoglycans in Breast Cancer: Friends and Foes.Biomolecules · 2025Review
- Neuron-specific Agrin splicing by Nova RNA-binding proteins regulates conserved neuromuscular junction development in chordates.PLoS biology · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Development and Application of a Cell-Based Assay for Detecting Anti-Agrin Antibodies Associated With Myasthenia Gravis.Journal of clinical neurology (Seoul, Korea) · 2025Article
- Congenital myasthenic syndromes a rare case of AGRN mutation.American journal of neurodegenerative disease · 2025Article
- A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv : the preprint server for biology · 2024Article
- Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.Nature communications · 2024Article
- Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study.Kidney diseases (Basel, Switzerland) · 2024Article
- Genetic and clinical evaluation of congenital myasthenic syndromes with long-term follow-up: experience of a tertiary center in Turkey.Acta neurologica Belgica · 2023Article
- New mutation in the β1 propeller domain of LRP4 responsible for congenital myasthenic syndrome associated with Cenani-Lenz syndrome.Scientific reports · 2023Article
- A mutation in DOK7 in congenital myasthenic syndrome forms aggresome in cultured cells, and reduces DOK7 expression and MuSK phosphorylation in patient-derived iPS cells.Human molecular genetics · 2023Article
- Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 13 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specimen showed a major disorganization of the neuromuscular junction, including changes in the nerve-terminal cytoskeleton and fragmentation of the synaptic gutters. Experiments performed in nonmuscle cells or in cultured C2C12 myotubes and using recombinant mini-agrin for the mutated and the wild-type forms showed that the mutated form did not impair the activation of MuSK or change the total number of induced acetylcholine receptor aggregates. A solid-phase assay using the dystrophin glycoprotein complex showed that the mutation did not affect the binding of agrin to alpha-dystroglycan. Injection of wild-type or mutated agrin into rat soleus muscle induced the formation of nonsynaptic acetylcholine receptor clusters, but the mutant protein specifically destabilized the endogenous neuromuscular junctions. Importantly, the changes observed in rat muscle injected with mutant agrin recapitulated the pre- and post-synaptic modifications observed in the patient. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.
Indexed as
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.