ArticleHuman molecular genetics2010
Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 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
- AGRN-, LRP4-, MUSK-Related CMS: Clinical, Neurophysiological, Morphological, Genetic and Pathological Mechanisms.Muscle & nerve · 2026Review
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Five key challenges for the plasma membrane insertion of nicotinic acetylcholine receptors in cellular model systems.Molecular and cellular biochemistry · 2026Review
- MuSK myasthenia gravis: from antigen-antibody to clinical translation.Frontiers in immunology · 2026Review
- Gene-specific response to muscle specific kinase agonist antibody in the treatment of congenital myasthenic syndromes.Brain communications · 2026Article
- Neuron-specific Agrin splicing by Nova RNA-binding proteins regulates conserved neuromuscular junction development in chordates.PLoS biology · 2025Article
- Whole Exome Sequencing Reveals Candidate Variants in Ion Channel Genes for Pelvic Muscle Dysfunction in Young Females with a Family History.International urogynecology journal · 2025Article
- A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv : the preprint server for biology · 2024Article
- MuSK Myasthenia Gravis-Potential Pathomechanisms and Treatment Directed against Specific Targets.Cells · 2024Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse.Biological reviews of the Cambridge Philosophical Society · 2021Review
- An improved method for culturing myotubes on laminins for the robust clustering of postsynaptic machinery.Scientific reports · 2020Article
- Congenital myasthenic syndrome due to mutations in MUSK suggests that the level of MuSK phosphorylation is crucial for governing synaptic structure.Human mutation · 2020Article
- Myasthenia Gravis: From the Viewpoint of Pathogenicity Focusing on Acetylcholine Receptor Clustering, Trans-Synaptic Homeostasis and Synaptic Stability.Frontiers in molecular neuroscience · 2020Article
- A Neonate With MuSK Congenital Myasthenic Syndrome Presenting With Refractory Respiratory Failure.Frontiers in pediatrics · 2020Article
- Disorders of FZ-CRD; insights towards FZ-CRD folding and therapeutic landscape.Molecular medicine (Cambridge, Mass.) · 2019Review
- Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.American journal of medical genetics. Part A · 2019Article
- Congenital Vocal Cord Paralysis and Late-Onset Limb-Girdle Weakness in MuSK-Congenital Myasthenic Syndrome.Frontiers in neurology · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We describe a severe congenital myasthenic syndrome (CMS) caused by two missense mutations in the gene encoding the muscle specific receptor tyrosine kinase (MUSK). The identified MUSK mutations M605I and A727V are both located in the kinase domain of MuSK. Intracellular microelectrode recordings and microscopy studies of the neuromuscular junction conducted in an anconeus muscle biopsy revealed decreased miniature endplate potential amplitudes, reduced endplate size and simplification of secondary synaptic folds, which were consistent with postsynaptic deficit. The study also showed a striking reduction of the endplate potential quantal content, consistent with additional presynaptic failure. Expression studies in MuSK deficient myotubes revealed that A727V, which is located within the catalytic loop of the enzyme, caused severe impairment of agrin-dependent MuSK phosphorylation, aggregation of acetylcholine receptors (AChRs) and interaction of MuSK with Dok-7, an essential intracellular binding protein of MuSK. In contrast, M605I, resulted in only moderate impairment of agrin-dependent MuSK phosphorylation, aggregation of AChRs and interaction of MuSK with Dok-7. There was no impairment of interaction of mutants with either the low-density lipoprotein receptor-related protein, Lrp4 (a co-receptor of agrin) or with the mammalian homolog of the Drosophila tumorous imaginal discs (Tid1). Our findings demonstrate that missense mutations in MUSK can result in a severe form of CMS and indicate that the inability of MuSK mutants to interact with Dok-7, but not with Lrp4 or Tid1, is a major determinant of the pathogenesis of the CMS caused by MUSK mutations.
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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.