ArticleProceedings of the National Academy of Sciences of the United States of America2001
Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 263 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Pooled it
- Convergent evidence that choline acetyltransferase gene variation is associated with prospective smoking cessation and nicotine dependence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Trial
- Pragmatic Phenotype-Electrophysiology-Genomics Integration in Pediatric Congenital Myasthenic Syndromes: Insights From 36 Patients in a Single-Center Study in China.CNS neuroscience & therapeutics · 2026Article
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Analysis of ligand recognition by choline O-acetyltransferase reveals thiol-reactive assay interference and weak ligand affinity in solution.The Journal of biological chemistry · 2026Article
- Molecular Diversity and Functional Implications of Mammalian Choline Acetyltransferases in Neuronal and Non-Neuronal Cells.International journal of molecular sciences · 2026Review
- Compound heterozygous CHAT gene mutations, a missense and a splice site variant, in two siblings with congenital myasthenic syndrome.Scientific reports · 2026Article
- The Central Cholinergic Synapse: A Primer.International journal of molecular sciences · 2025Review
- Neonatal Congenital Myasthenic Syndrome Linked to CHAT Gene Variants: A Case Report and Treatment Insights.The American journal of case reports · 2025Article
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Congenital myasthenic syndrome secondary to pathogenic variants in the SLC5A7 gene: report of two cases.BMC medical genomics · 2024Article
- Mild phenotype ofFrontiers in pediatrics · 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
- The Importance of Early Treatment of Inherited Neuromuscular Conditions.Journal of neuromuscular diseases · 2024Review
- Exome Sequencing and Optical Genome Mapping in Molecularly Unsolved Cases of Duchenne Muscular Dystrophy: Identification of a Causative X-Chromosomal Inversion Disrupting theInternational journal of molecular sciences · 2023Article
- 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
- Potential revival of cholinesterase inhibitors as drugs in veterinary medicine.Frontiers in veterinary science · 2023Review
- Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Choline acetyltransferase (ChAT; EC ) catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. Mutations in genes encoding ChAT affecting motility exist in Caenorhabditis elegans and Drosophila, but no CHAT mutations have been observed in humans to date. Here we report that mutations in CHAT cause a congenital myasthenic syndrome associated with frequently fatal episodes of apnea (CMS-EA). Studies of the neuromuscular junction in this disease show a stimulation-dependent decrease of the amplitude of the miniature endplate potential and no deficiency of the ACh receptor. These findings point to a defect in ACh resynthesis or vesicular filling and to CHAT as one of the candidate genes. Direct sequencing of CHAT reveals 10 recessive mutations in five patients with CMS-EA. One mutation (523insCC) is a frameshifting null mutation. Three mutations (I305T, R420C, and E441K) markedly reduce ChAT expression in COS cells. Kinetic studies of nine bacterially expressed ChAT mutants demonstrate that one mutant (E441K) lacks catalytic activity, and eight mutants (L210P, P211A, I305T, R420C, R482G, S498L, V506L, and R560H) have significantly impaired catalytic efficiencies.
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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.