ArticleHuman mutation2016
Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating.
Article in Human mutation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports.Current neuropharmacology · 2021Pooled it
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Article
- Congenital myasthenic syndromes in a Southeast Asian adult neurology clinic: a long road to diagnosis and therapy.BMC neurology · 2026Article
- Article
- Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.Brain : a journal of neurology · 2024Article
- Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit.Journal of neuromuscular diseases · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Homozygous Duplication in theBiomedicines · 2023Article
- Vocal Cord Paralysis and Feeding Difficulties as Early Diagnostic Clues of Congenital Myasthenic Syndrome with Neonatal Onset: A Case Report and Review of Literature.Journal of personalized medicine · 2023Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Rare slow channel congenital myasthenic syndromes without repetitive compound muscle action potential and dramatic response to low dose fluoxetine.Acta neurologica Belgica · 2021Article
- Determinants of the repetitive-CMAP occurrence and therapy efficacy in slow-channel myasthenia.Neurology · 2020Article
- [Advances in the diagnosis and treatment of congenital myasthenic syndrome].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- Mitochondrial disorder mimicking rheumatoid disease.Zeitschrift fur Rheumatologie · 2019Article
- Slow-channel myasthenia due to novel mutation in M2 domain of AChR delta subunit.Annals of clinical and translational neurology · 2019Article
- [Congenital myasthenic syndromes in adulthood : Challenging, rare but treatable].Der Nervenarzt · 2019Review
- Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients.Journal of neurology · 2018Article
- High Throughput Random Mutagenesis and Single Molecule Real Time Sequencing of the Muscle Nicotinic Acetylcholine Receptor.PloS one · 2016Article
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9 authors.
Funding
Abstract
We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.
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