Evidence map›Paper›PMID 40393460›Full record

ArticleAmerican journal of human genetics2025

Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range.

Stacy G Guzman, Sarah M Ruggiero, Shiva Ganesan, Colin A Ellis, Alicia G Harrison, Katie R Sullivan, Zornitza Stark, Natasha J Brown, Sajel L Kana, Anabelle Tuttle and 29 more

Abstract read
In one paragraph

Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Beyond the synapse: Bassoon mutations drive epilepsy through Astrocyte-Neuron crosstalk.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

39 authors.

Stacy G GuzmanDepartment of Biochemistry, Biophysics, and Chemical Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Sarah M RuggieroThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Shiva GanesanThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Colin A EllisThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Alicia G HarrisonThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Katie R SullivanThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Zornitza StarkAustralian Genomics, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
Natasha J BrownAustralian Genomics, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
Sajel L KanaDivision of Clinical Genetics, Genomics, and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA.
Anabelle TuttleGeneDx, Gaithersburg, MD, USA.
Jair TenorioInstituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, 28046 Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Pablo LapunzinaInstituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, 28046 Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Julián NevadoInstituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, 28046 Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; ERN-ITHACA-European Reference Network, Madrid, Spain.
Marie T McDonaldDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Courtney JensenChildren's Services, Duke University Health Center, Duke University, Durham, NC, USA.
Patricia G WheelerPediatric Genetics Specialty Practice, Arnold Palmer Hospital for Children, Orlando, FL, USA.
Lila StangePediatric Genetics Specialty Practice, Arnold Palmer Hospital for Children, Orlando, FL, USA.
Jennifer MorrisonPediatric Genetics Specialty Practice, Arnold Palmer Hospital for Children, Orlando, FL, USA.
Boris KerenDepartment of Genetics, La Pitié-Salpêtrière Hospital, APHP, Sorbonne University, Paris, France.
Solveig HeideCytogenetics Department, Cochin Hospital, Assistance Publique des Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Medical School, Paris, France.
Meg W KeatingGreenwood Genetics Center, Greenwood, SC, USA.
Kameryn M ButlerGreenwood Genetics Center, Greenwood, SC, USA.
Mike A LyonsGreenwood Genetics Center, Greenwood, SC, USA; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State Universitygrid.47894.36, Fort Collins, CO, USA.
Shailly JainDepartment of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Mehdi YeganehDivision of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Centre Hospitalier Universitaire de Québec, Centre Mère-Enfant Soleil Université Laval, Québec City, QC, Canada.
Michelle L ThompsonDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Molly SchroederDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Molecular and Human Genetics, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Hoanh NguyenDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Molecular and Human Genetics, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Jorge GranadilloDivision of Molecular and Human Genetics, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Kari M JohnstonDepartment of Genetics and Metabolism, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Chaya N MuraliDepartment of Genetics and Metabolism, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Katie BosankoSection of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
T Andrew BurrowSection of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
CHOP Birth Defects Biorepository
Penn Medicine BioBank
Syreeta MorganCenter for Applied Genomics, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Deborah J WatsonCenter for Applied Genomics, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hakon HakonarsonCenter for Applied Genomics, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ingo HelbigDepartment of Biochemistry, Biophysics, and Chemical Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA; Epilepsy and Neurodevelopmental Disorders Center (ENDD), Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ihelbig@email.chop.edu.

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
A computational phenotyping approach to characterize neurogenetic disordersR01NS131512 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Ingo Helbig · 2023 to 2026
$2.8M
Subgroup delineation in genetic epilepsies and developmental brain disordersR01NS127830 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Ingo Helbig · 2023 to 2026
$2.8M
ClinGen Expert Curation Panel for the EpilepsiesU24NS120854 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ingo Helbig, HEATHER C. MEFFORD · 2021 to 2026
$2.0M
Polygenic risk in familial epilepsyK23NS121520 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ELLIS, COLIN · 2021 to 2025
$1.1M
NCATS NIH HHS UL1 TR001878NINDS NIH HHS K23 NS121520NINDS NIH HHS R01 NS127830NINDS NIH HHS R01 NS131512NINDS NIH HHS U24 NS120854
6 · The paper itself

Abstract

Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders (NDDs) and epilepsy. Here, we describe 14 individuals with de novo disruptive variants in BSN, which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks. Clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29, 45%), febrile seizures (7/29, 25%), generalized tonic-clonic seizures (5/29, 17%), and focal-onset seizures (3/29, 10%). Behavioral phenotypes were present in almost half of all individuals (14/29, 48%), which included ADHD (7/29, 25%) and autistic behavior (5/29, 17%). Additional common features included developmental delay (11/29, 38%), obesity (10/29, 34%), and delayed speech (8/29, 28%). In adults with BSN PTVs, milder features were common, suggesting phenotypic variability, including a range of individuals without obvious neurodevelopmental features (7/29, 24%). To detect gene-specific signatures, we performed association analysis in a cohort of 14,895 individuals with NDDs. A total of 66 clinical features were associated with BSN, including febrile seizures (p = 1.26e-06) and behavioral disinhibition (p = 3.39e-17). Furthermore, individuals carrying BSN variants were phenotypically more similar than expected by chance (p = 0.00014), exceeding phenotypic relatedness in 179/256 NDD-related conditions. In summary, integrating information derived from community-based gene matching and large data repositories through computational phenotyping approaches, we identify BSN variants as the cause of a synaptic disorder with a broad phenotypic range across the age spectrum.

Indexed as

Nerve Tissue ProteinsNeurodevelopmental DisordersAdolescentAdultChildChild, PreschoolEpilepsyFemaleHumansMaleMiddle AgedPhenotypeSeizures, FebrileYoung AdultNerve Tissue ProteinsBSNdevelopmental and epileptic encephalopathyepilepsygeneticshuman phenotype ontologylongitudinal EMR analysisneurodevelopmental disorders

Identifiers

PMID40393460
PMCPMC12256794

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