ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
DLG4-related synaptopathy: a new rare brain disorder.
Open access · bronzeAbstract read
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. Cited by 45 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% of its field
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.
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.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Ketogenic Diet-Associated Remodeling of the Cortical Proteome in Rats With Genetic Absence Epilepsy.Brain and behavior · 2026Article
- Article
- Article
- Biochemically Constrained Multi-Omics Integration Reveals Protein-Metabolite Dependencies Across Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- A patient-derived mouse model reproduces molecular, neurological, and sleep symptoms of SHINE syndrome.Human molecular genetics · 2026Article
- A Synonymous DLG4 Variant (c.771G>A) Causes Exon 9 Skipping via Paternal Germline Mosaicism in DLG4-Related Synaptopathy.Molecular genetics & genomic medicine · 2026Article
- Multi-omics profiling reveals MAGEL2-driven defects in human corticogenesis shared across Prader-Willi and Schaaf-Yang syndromes.bioRxiv : the preprint server for biology · 2026Article
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- A data-driven framework linking the connectome to spatial gene expression gradients inspired by chemoaffinity theory.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synapse types are spatially associated with regional hemodynamics in the mouse brain.PLoS biology · 2026Article
- hiPSC-derived cortical neurons from ADHD individuals reveal dysregulated glutamatergic development.Molecular psychiatry · 2026Article
- DLG4-Related Synaptopathy and Coexisting Fabry's Disease: A Case Report.Annals of Indian Academy of Neurology · 2026Article
- DHA-dominant Omega-3 compositions enhance PSD-95 organization and glutamatergic protein expression.Frontiers in synaptic neuroscience · 2026Article
- Visual Function Characteristics inJournal of clinical medicine · 2025Article
- A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans.Molecular biology and evolution · 2025Article
- MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Autoantibody profiling of autism spectrum disorder patients with monoamine oxidase a deficiency.Brain, behavior, & immunity - health · 2025Article
- Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range.American journal of human genetics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
86 authors at 20 institutions in 14 countries.
Agustí Rodríguez-PalmeroNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Melissa Maria BoerrigterKennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
David Gómez-AndrésChild Neurology Unit. Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Kimberly A AldingerCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Íñigo Marcos-AlcaldeMolecular Modelling Group, Severo Ochoa Molecular Biology Centre (CBM SO, CSIC-UAM), Madrid, Spain.
Bernt PoppInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
David B EvermanGreenwood Genetic Center, Greenwood, SC, USA.
Alysia Kern LovgrenBroad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephanie ArpinService de génétique, CHU de Tours, UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
Vahid BahrambeigiGreenwood Genetic Center, Greenwood, SC, USA.
Gea BeundersDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Anne-Marie BisgaardCenter for Rett syndrome, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark.
V A BjerregaardKennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Ange-Line BruelINSERM UMR1231, GAD, University of Burgundy, FHU-TRANSLAD, CHU Dijon-Bourgogne, Dijon, France.
Thomas D ChallmanGeisinger Autism & Developmental Medicine Institute, Lewisburg, PA, USA.
Benjamin CognéService de Génétique Médicale, CHU Nantes, Nantes, France.
Christine CoubesDépartement de Génétique Médicale, Maladies rares et Médecine personnalisée, CHU Montpellier, France.
Stella A de ManDepartment of Pediatrics, Amphia Hospital, Breda, The Netherlands.
Anne-Sophie Denommé-PichonINSERM UMR1231, GAD, University of Burgundy, FHU-TRANSLAD, CHU Dijon-Bourgogne, Dijon, France.
Thomas J DyeDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Frances ElmslieSouth West Thames Regional Genetics Service, St George's University Hospitals, University of London, London, United Kingdom.
Lars FeukScience for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Sixto García-MiñaúrInstitute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.
Tracy GertlerDivision of Neurology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Elisa GiorgioDepartment of Medical Sciences, University of Turin, Torino, Italy.
Nicolas GruchyService de Génétique, CHU Caen Clemenceau, Biotargen, Univ Caen, France.
Tobias B HaackInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Chad R Haldeman-EnglertMission Fullerton Genetics Center, Asheville, NC, USA.
Bjørn Ivar HaukanesDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Juliane HoyerInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Anna C E HurstDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Bertrand IsidorService de Génétique Médicale, CHU Nantes, Nantes, France.
Maria Johansson SollerDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Sulagna KusharyInstitute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Malin KvarnungDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Yuval E LandauLeumit Health Care Services, Tel-Aviv, Israel.
Kathleen A LeppigGenetic Services, Kaiser Permanente of Washington, Seattle, WA, USA.
Anna LindstrandDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Lotte KleinendorstDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Alex MacKenzieChildren's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada.
Giorgia MandrileThalassemia Centre and Genetic Unit, San Luigi University Hospital, Orbassano, Italy.
Bryce A MendelsohnDepartment of Pediatrics, Division of Medical Genetics, University of California, San Francisco, CA, USA.
Setareh MoghadasiDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Jenny E MortonWest Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Birmingham Women's Hospital, Birmingham, United Kingdom.
Sebastien MouttonINSERM UMR1231, GAD, University of Burgundy, FHU-TRANSLAD, CHU Dijon-Bourgogne, Dijon, France.
Amelie J MüllerInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Melanie O'LearyBroad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Marta Pacio-MíguezInstitute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.
Maria Palomares-BraloInstitute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.
Sumit ParikhMitochondrial Medicine & Neurogenetics, Cleveland Clinic, Cleveland, OH, USA.
Rolph PfundtGenomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
Ben Pode-ShakkedSackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Anita RauchInstitute of Medical Genetics, University of Zurich, Schlieren, Switzerland.
Elena RepnikovaDivision of Clinical Laboratory Genetics & Genomics, Children's Mercy Hospital, Kansas City, MO, USA.
Anya Revah-PolitiDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Meredith J RossDepartment of Pediatrics, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA.
Claudia A L RuivenkampDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Elisabeth SarrazinCentre de Référence des Maladies rares neuromusculaires AOC, Hôpital Pierre Zobda Quitman, CHU Martinique, Fort de France, Martinique.
Juliann M SavattGeisinger Autism & Developmental Medicine Institute, Lewisburg, PA, USA.
Agatha SchlüterNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Bitten Schönewolf-GreulichKennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Zohra ShadCook Children's Medical Center Genetics, Fort Worth, TX, USA.
Charles Shaw-SmithDepartment of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
Joseph T ShiehInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
Motti ShohatBioinformatics unit, Cancer Research Center, Sheba Medical Center and Sackler Medical Center, Tel Aviv University and Maccabi HMO, Tel Aviv, Israel.
Stephanie SprangerPraxis fuer Humangenetik, Klinikum Bremen-Mitte, Bremen, Germany.
Heidi ThieseGenetic Services, Kaiser Permanente of Washington, Seattle, WA, USA.
Frederic Tran Mau-ThemINSERM UMR1231, GAD, University of Burgundy, FHU-TRANSLAD, CHU Dijon-Bourgogne, Dijon, France.
Bregje van BonDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Ineke van de BurgtDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Ingrid M B H van de LaarDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Esmée van DrieDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Mieke M van HaelstDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Conny M van Ravenswaaij-ArtsDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Edgard VerduraNeurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Antonio VitobelloINSERM UMR1231, GAD, University of Burgundy, FHU-TRANSLAD, CHU Dijon-Bourgogne, Dijon, France.
Stephan WaldmüllerInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Sharon WhitingChildren's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada.
Christiane ZweierInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Carlos E PradaDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Bert B A de VriesDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
William B DobynsCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Simone F ReiterDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Paulino Gómez-PuertasMolecular Modelling Group, Severo Ochoa Molecular Biology Centre (CBM SO, CSIC-UAM), Madrid, Spain.
Aurora Pujol *Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Zeynep Tümer *Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Zeynep.tumer@regionh.dk.ORCID http://orcid.org/0000-0002-4777-5802
Inserm · FRRadboud University Nijmegen · NLAmsterdam University Medical Centers · NLCopenhagen University Hospital · DKFriedrich-Alexander-Universität Erlangen-Nürnberg · DEHospital Universitario La Paz · ESKarolinska University Hospital · SETel Aviv University · ILUniversity of Tübingen · DEAutism & Developmental Medicine Institute · USBroad Institute · USCentre National de la Recherche Scientifique · FRCincinnati Children's Hospital Medical Center · USHaukeland University Hospital · NOInstitut d'Investigació Biomédica de Bellvitge · ESKaiser Permanente · USLeiden University Medical Center · NLUniversity Medical Center Groningen · NLUniversity of California, San Francisco · USUniversity of Ottawa · CA
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MNHGRI NIH HHS UM1 HG008900
Abstract
purposePostsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.
methodsThe clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.
resultsThe clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.
conclusionThe present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
Indexed as
Autism Spectrum DisorderBrain DiseasesIntellectual DisabilityNeurodevelopmental DisordersBrainDisks Large Homolog 4 ProteinHumansPhenotypeDisks Large Homolog 4 ProteinDLG4 protein, human
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
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.