Evidence map›Paper›PMID 27590285›Full record

ArticleNeurology2016

Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.

Gina L O'Grady, Corien Verschuuren, Michaela Yuen, Richard Webster, Manoj Menezes, Johanna M Fock, Natalie Pride, Heather A Best, Tatiana Benavides Damm, Christian Turner and 7 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

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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.

2 · The registry

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3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019
    Pooled it
  2. Review
  3. Review
  4. Review
  5. The Central Cholinergic Synapse: A Primer.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
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  14. ΔInternational journal of molecular sciences · 2023
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4 · The record

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5 · Who and what money

Authors and funding

17 authors at 8 institutions in 3 countries.

Gina L O'GradyFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Corien VerschuurenFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Michaela YuenFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Richard WebsterFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Manoj MenezesFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Johanna M FockFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Natalie PrideFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Heather A BestFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Tatiana Benavides DammFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Christian TurnerFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Monkol LekFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Andrew G EngelFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Kathryn N NorthFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Nigel F ClarkeFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Daniel G MacArthurFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Erik-Jan KamsteegFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands.
Sandra T CooperFrom the Institute for Neuroscience and Muscle Research (G.L.O., M.Y., N.P., H.A.B., T.B.D., K.N.N., N.F.C., S.T.C.), Kids Research Institute, T.Y. Department of Neurology (M.M., R.W.), and Heart Centre for Children (C.T.), Children's Hospital at Westmead, Sydney; Discipline of Paediatrics and Child Health (G.L.O., M.M., H.A.B., K.N.N., N.F.C., S.T.C.), Faculty of Medicine, University of Sydney, Australia; Departments of Genetics (C.V.) and Child Neurology (J.M.F.), University of Groningen University Medical Center Groningen, the Netherlands; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; Broad Institute of Harvard and Massachusetts Institute of Technology (M.L., D.G.M.), Cambridge; Department of Neurology (A.G.E.), Mayo Clinic, Rochester, MN; Murdoch Children's Research Institute (K.N.N.), Royal Children's Hospital, Victoria, Australia; and Department of Human Genetics (E.-J.K.), Radboud University Medical Center, Nijmegen, the Netherlands. Sandra.cooper@sydney.edu.au.
Murdoch Children's Research Institute · AUUniversity of Sydney · AUBroad Institute · USMassachusetts Institute of Technology · USMayo Clinic in Arizona · USRoyal Children's Hospital · AUUniversity Medical Center Groningen · NLUniversity of Groningen · NL

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
NHGRI NIH HHS U54 HG003067NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

objectiveTo describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3.

methodsIndividuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter (VAChT), through whole-exome sequencing.

resultsThe patients demonstrated features seen in presynaptic congenital myasthenic syndrome, including ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water for patient 1. Both patients demonstrated moderate clinical improvement on pyridostigmine. Patient 1 had a broader phenotype, including learning difficulties and left ventricular dysfunction. Electrophysiologic studies were typical for a presynaptic defect. Both patients showed profound electrodecrement on low-frequency repetitive stimulation followed by a prolonged period of postactivation exhaustion. In patient 1, this was unmasked only after isometric contraction, a recognized feature of presynaptic disease, emphasizing the importance of activation procedures.

conclusionsVAChT is responsible for uptake of acetylcholine into presynaptic vesicles. The clinical and electrographic characteristics of the patients described are consistent with previously reported mouse models of VAChT deficiency. These findings make it very likely that defects in VAChT due to variants in SLC18A3 are a cause of congenital myasthenic syndrome in humans.

Indexed as

Genetic VariationAdolescentChildDiagnosis, DifferentialFemaleHumansMaleMyasthenic Syndromes, CongenitalVesicular Acetylcholine Transport ProteinsSLC18A3 protein, humanVesicular Acetylcholine Transport Proteins

Identifiers

PMID27590285
PMCPMC5075972
OpenAlexW2515611666

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