Evidence map›Paper›PMID 33299146›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Chiara Klöckner, Heinrich Sticht, Pia Zacher, Bernt Popp, Holly E Babcock, Dewi P Bakker, Katy Barwick, Michaela V Bonfert, Carsten G Bönnemann, Eva H Brilstra and 49 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 46 citations in OpenAlex.

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  11. Review
  12. Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Allelic heterogeneity and abnormal vesicle recycling inFrontiers in molecular neuroscience · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Genetic disorders of neurotransmitter release machinery.Frontiers in synaptic neuroscience · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

59 authors at 20 institutions in 9 countries.

Chiara KlöcknerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Heinrich StichtInstitute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Pia ZacherThe Saxon Epilepsy Center Kleinwachau, Radeberg, Germany.
Bernt PoppInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Holly E BabcockRare Disease Institute, Children's National Hospital, Washington, DC, USA.
Dewi P BakkerDepartment of Child Neurology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Katy BarwickInstitute of Child Health, University Collge London, London, UK.
Michaela V BonfertDepartment of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children's Hospital, LMU - University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Eva H BrilstraDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Care4Rare Canada Consortium
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA.
Angus J ClarkeDivision of Cancer & Genetics, School of Medicine, Cardiff University, Wales, UK.
Patrick DevineDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Jamie L FraserRare Disease Institute, Division of Genetics and Metabolism, Children's National Hospital, Washington, DC, USA.
Jennifer FriedmanDepartments of Neurosciences and Pediatrics, University of California San Diego and Division of Neurology, Rady Children's Hospital, San Diego, CA, USA.
Alyssa GatesDepartment of Genetic Services, Kaiser Permanente Washington, Seattle, WA, USA.
Jamal GhoumidService de Génétique Clinique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France.
Emma HobsonYorkshire Clinical Genetics Service, Chapel Allerton Hospital, Leeds, UK.
Gabriella HorvathDepartment of Pediatrics, Division of Biochemical Diseases, University of British Columbia, Vancouver, Canada.
Jennifer Keller-RameyGeneDx, Gaithersburg, MD, USA.
Boris KerenAPHP, Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
Manju A KurianInstitute of Child Health, University Collge London, London, UK.
Virgina LeeDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Kathleen A LeppigDepartment of Genetic Services, Kaiser Permanente Washington, Seattle, WA, USA.
Johan LundgrenInstitute of Clinical Sciences, Skane University Hospital, Lund, Sweden.
Marie T McDonaldDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Heather M McLaughlinInvitae Corporation, San Francisco, CA, USA.
Amy McTagueInstitute of Child Health, University Collge London, London, UK.
Heather C MeffordDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Cyril MignotDépartement de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et Hôpital Trousseau, APHP, Sorbonne Université, Paris, France.
Mohamad A MikatiDivision of Pediatric Neurology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Caroline NavaSorbonne University, Paris Brain Institute, Inserm U1127, CNRS UMR 7225, AP-HP, Pitié Salpêtrière Hospital, Department of Genetics, Paris, France.
F Lucy RaymondNIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Julian R SampsonDivision of Cancer & Genetics, School of Medicine, Cardiff University, Wales, UK.
Alba Sanchis-JuanNIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Joseph T C ShiehDivision of Medical Genetics, University of California, San Francisco, San Francisco, CA, USA.
Marwan ShinawiDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Anne SlavotinekDivision of Medical Genetics, University of California, San Francisco, San Francisco, CA, USA.
Tommy StödbergDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Nicholas StongInstitute for Genomic Medicine, Columbia University, New York, NY, USA.
Jennifer A SullivanDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Ashley C TaylorSection of Genetics, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Tomi L TolerDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Marie-José van den BoogaardDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Saskia N van der CrabbenDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Koen L I van GassenDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Richard H van JaarsveldDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Jessica Van ZiffleDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Alexandrea F WadleyUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Matias WagnerInstitute of Neurogenomics, Helmholtz Zentrum Munich, Neuherberg, Germany.
Kristen WigbyDepartment of Pediatrics, Division of Genetics, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, CA, USA.
Saskia B WortmannAmalia Children's Hospital, Radboud University Nijmegen, Nijmegen, The Netherlands.
Yuri A ZarateSection of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Rikke S MøllerInstitute for Regional Health Services, University of Southern Denmark, Odense, Denmark.
Johannes R LemkeInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany. konrad.platzer@medizin.uni-leipzig.de.ORCID http://orcid.org/0000-0001-6127-6308
University of California, San Francisco · USDuke Medical Center · USLeipzig University · DEUniversity Medical Center Utrecht · NLUniversity College London · GBAmsterdam University Medical Centers · NLCardiff University · GBChildren's National · USKaiser Permanente · USNational Institutes of Health · USSorbonne Université · FRUniversity of Oklahoma Health Sciences Center · USWashington University in St. Louis · USCentre Hospitalier Universitaire de Lille · FRCentre National de la Recherche Scientifique · FRChapel Allerton Hospital · GBChildren’s Institute · USColumbia University · USColumbia University Irving Medical Center · USEpilepsiezentrum Kleinwachau Gemeinnützige · DE

Funding

Molecular and Clinical Manifestations of Matrix and Aggregate MyopathiesZIANS003129 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BÖNNEMANN, CARSTEN · 2011 to 2025
$52.8M
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Sharing Aggregate Genomics Research Findings with Diverse Participants: A Pilot Study of an Innovative Design StrategyU01HG009599 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOENIG, BARBARA A., KWOK, PUI-YAN · 2017 to 2021
$16.3M
CIHRDepartment of Health RG65966Department of Health RP-2016-07-019Medical Research Council MR/T007087/1NHGRI NIH HHS U01 HG009599NHGRI NIH HHS UM1 HG008900Wellcome Trust
6 · The paper itself

Abstract

purposeThis study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals.

methodsIndividuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed.

resultsThe cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex.

conclusionWe provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed "SNAREopathies."

Indexed as

Brain DiseasesEpilepsyIntellectual DisabilityNeurodevelopmental DisordersChild, PreschoolHumansPhenotypeSynaptosomal-Associated Protein 25SNAP25 protein, humanSynaptosomal-Associated Protein 25

Identifiers

PMID33299146
OpenAlexW3111381539

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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.