SynthesisPLoS genetics2014
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 373 papers, 7 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
373citing papers in PubMed, 7 pooled it
32.9field-weighted citation impact, top 1% of its field
What it found
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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.
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
373 citing papers in PubMed, 7 syntheses or guidelines pooled it, 654 citations in OpenAlex.
- Pooled it
- Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review.Nutrients · 2023Pooled it
- Pooled it
- Genome-wide association study meta-analysis of suicide death and suicidal behavior.Molecular psychiatry · 2023Pooled it
- Meta-analysis of epigenome-wide association studies of major depressive disorder.Scientific reports · 2022Pooled it
- A systematic review of common genetic variation and biological pathways in autism spectrum disorder.BMC neuroscience · 2021Pooled it
- Genetic risk factors for autism-spectrum disorders: a systematic review based on systematic reviews and meta-analysis.Journal of neural transmission (Vienna, Austria : 1996) · 2021Pooled it
- A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome.Molecular autism · 2021Trial
- Effects of early-life tactile experience enrichment on autistic-like behaviors and synaptic alterations inFundamental research · 2026Article
- Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.Brain sciences · 2026Review
- Inflammation increases the penetrance of behavioral impairment in Shank3 haploinsufficiency mice - can it explain the behavioral regression in Autism?Molecular psychiatry · 2026Article
- Evaluation of Lead exposure's link to autism-like behavior and Shank 3 gene expression in C57BL/6J mice.The Journal of veterinary medical science · 2026Article
- Prevalence of Phelan McDermid Syndrome Estimated To Be ~1:7300 Using a Multisource Model.Autism research : official journal of the International Society for Autism Research · 2026Article
- Restless senses, restless sleep: Exploring the sensory-sleep link in Phelan-McDermid syndrome. A Cross-Sectional Exploratory Study.BMC pediatrics · 2026Article
- Article
- Social Novelty Recruits a Dysfunctional Nucleus Accumbens Ensemble That Drives Social Avoidance in abioRxiv : the preprint server for biology · 2026Article
- "SHANK3 deficiency alters early progenitor dynamics and reveals shared pathways with neurodegeneration".Molecular psychiatry · 2026Article
- Chromosome 22q13 terminal deletion size is associated with relevant clinical features in a sample of 63 Italian patients with Phelan-McDermid syndrome.Journal of neurodevelopmental disorders · 2026Article
- Review
- Dynamic recruitment of CaMKII into SHANK3 phase-separated condensates tunes postsynaptic density remodeling during long-term potentiation.Nature communications · 2026Article
313 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
60 authors at 20 institutions in 7 countries.
Claire S LeblondInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Caroline NavaINSERM U975 - CRICM, Institut du cerveau et de la moelle épinière (ICM), CNRS 7225 - CRICM, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; UMR_S 975, Paris, France.
Anne PolgeLaboratoire de Biochimie, CHU Nîmes, Nîmes, France.
Julie GauthierMolecular Diagnostic Laboratory and Division of Medical Genetics, CHU Sainte-Justine, Montreal, Quebec, Canada.
Guillaume HuguetInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Serge LumbrosoLaboratoire de Biochimie, CHU Nîmes, Nîmes, France.
Fabienne GiulianoDepartment of Medical Genetics, Nice Teaching Hospital, Nice, France.
Coline StordeurInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Department of Child and Adolescent Psychiatry, Paris, France.
Christel DepienneINSERM U975 - CRICM, Institut du cerveau et de la moelle épinière (ICM), CNRS 7225 - CRICM, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; UMR_S 975, Paris, France.
Kevin MouzatLaboratoire de Biochimie, CHU Nîmes, Nîmes, France.
Dalila PintoDepartments of Psychiatry, Genetics and Genomic Sciences, Seaver Autism Center, The Mindich Child Health & Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Jennifer HoweThe Centre for Applied Genomics, The Hospital for Sick Children and the University of Toronto McLaughlin Centre, Toronto, Canada.
Nathalie LemièreInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Christelle M DurandInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Jessica GuibertInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Elodie EyInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Roberto ToroInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Hugo PeyreLaboratoire de Sciences Cognitives et Psycholinguistique, École Normale Supérieure, CNRS, EHESS, Paris, France.
Alexandre MathieuInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
Frédérique AmsellemInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Department of Child and Adolescent Psychiatry, Paris, France; FondaMental Foundation, Créteil, France.
Maria RastamDepartment of Clinical Sciences in Lund, Lund University, Lund, Sweden.
I Carina GillbergGillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
Gudrun A RappoldDepartment of Molecular Human Genetics, Heidelberg University, Heidelberg, Germany.
Richard HoltWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Anthony P MonacoWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Elena MaestriniDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Pilar GalanNutritional Epidemiology Research Unit, INSERM U557, INRA U1125, CNAM, University of Paris 13, CRNH IdF, Bobigny, France.
Delphine HeronAssistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique, Unité fonctionnelle de génétique clinique, Paris, France; Centre de Référence "Déficiences intellectuelles de causes rares", Paris, France and Groupe de Recherche Clinique "Déficience intellectuelle et autisme", UPMC, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Service de Neuropédiatrie, Paris, France.
Aurélia JacquetteAssistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique, Unité fonctionnelle de génétique clinique, Paris, France; Centre de Référence "Déficiences intellectuelles de causes rares", Paris, France and Groupe de Recherche Clinique "Déficience intellectuelle et autisme", UPMC, Paris, France.
Alexandra AfenjarAssistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique, Unité fonctionnelle de génétique clinique, Paris, France; Centre de Référence "Déficiences intellectuelles de causes rares", Paris, France and Groupe de Recherche Clinique "Déficience intellectuelle et autisme", UPMC, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Service de Neuropédiatrie, Paris, France.
Agnès RastetterINSERM U975 - CRICM, Institut du cerveau et de la moelle épinière (ICM), CNRS 7225 - CRICM, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; UMR_S 975, Paris, France.
Alexis BriceINSERM U975 - CRICM, Institut du cerveau et de la moelle épinière (ICM), CNRS 7225 - CRICM, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; UMR_S 975, Paris, France.
Françoise DevillardDépartement de génétique et procréation, Hôpital Couple-Enfant, Grenoble, France.
Brigitte AssoulineCADIPA, Centre de Ressources Autisme Rhône-Alpes, Saint Egrève, France.
Fanny LaffargueService de Génétique Médicale, Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, France.
James LespinasseUF de Génétique Chromosomique, Centre Hospitalier de Chambéry - Hôtel-dieu, Chambéry, France.
Jean ChiesaUF de Cytogénétique et Génétique Médicale, Hôpital Caremeau, Nîmes, France.
François RivierCHRU Montpellier, Neuropédiatrie CR Maladies Neuromusculaires, Montpellier, France; U1046, INSERM, Université Montpellier 1 et 2, Montpellier, France.
Dominique BonneauLUNAM Université, INSERM U1083 et CNRS UMR 6214, Angers, France; Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France.
Beatrice RegnaultEukaryote Genotyping Platform, Genopole, Institut Pasteur, Paris, France.
Diana ZelenikaCentre National de Génotypage, Evry, France.
Marc DelepineCentre National de Génotypage, Evry, France.
Mark LathropCentre National de Génotypage, Evry, France.
Damien SanlavilleHospices Civils de Lyon, CHU de Lyon, Départment de Génétique, Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Claude Bernard Lyon I University, Bron, France.
Caroline Schluth-BolardHospices Civils de Lyon, CHU de Lyon, Départment de Génétique, Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Claude Bernard Lyon I University, Bron, France.
Patrick EderyHospices Civils de Lyon, CHU de Lyon, Départment de Génétique, Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Claude Bernard Lyon I University, Bron, France.
Laurence PerrinAssistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Genetic department, Cytogenetic Unit, Paris, France.
Anne Claude TabetAssistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Genetic department, Cytogenetic Unit, Paris, France.
Michael J SchmeisserInstitute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
Tobias M BoeckersInstitute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
Mary ColemanFoundation for Autism Research, Sarasota, Florida, United States of America.
Daisuke SatoThe Centre for Applied Genomics, The Hospital for Sick Children and the University of Toronto McLaughlin Centre, Toronto, Canada.
Peter SzatmariThe Centre for Applied Genomics, The Hospital for Sick Children and the University of Toronto McLaughlin Centre, Toronto, Canada.
Stephen W SchererThe Centre for Applied Genomics, The Hospital for Sick Children and the University of Toronto McLaughlin Centre, Toronto, Canada.
Guy A RouleauMontreal Neurological Institute, McGill University, Montreal, Canada.
Catalina BetancurSorbonne Universités, UPMC Univ Paris 6, Paris, France; INSERM U1130, Paris, France; CNRS UMR 8246, Paris, France.
Marion LeboyerFondaMental Foundation, Créteil, France; INSERM U955, Psychiatrie Génétique, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; Assistance Publique-Hôpitaux de Paris, DHU PePSY, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires Henri Mondor, Créteil, France.
Christopher GillbergGillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden; Institute of Child Health, University College London, London, United Kingdom.
Richard DelormeInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Department of Child and Adolescent Psychiatry, Paris, France; FondaMental Foundation, Créteil, France.
Thomas BourgeronInstitut Pasteur, Human Genetics and Cognitive Functions Unit, Paris, France; CNRS UMR 3571 Genes, Synapses and Cognition, Institut Pasteur, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France; FondaMental Foundation, Créteil, France.
Université Paris Cité · FRAssistance Publique – Hôpitaux de Paris · FRCentre Hospitalier Universitaire de Nîmes · FRCentre National de la Recherche Scientifique · FRCentre National de Recherche en Génomique Humaine · FRDélégation Paris 7 · FRInstitut Pasteur · FRUniversity of Toronto · CAHôpital Robert-Debré · FRInserm · FRSorbonne Paris Cité · FRSorbonne Université · FRUniversität Ulm · DECentre for Human Genetics · GBCentre Hospitalier Métropole Savoie · FRCentre Hospitalier Universitaire d'Angers · FRCentre Hospitalier Universitaire de Clermont-Ferrand · FRCentre Hospitalier Universitaire de Nice · FRCentre Hospitalier Universitaire Sainte-Justine · CAÉcole des hautes études en sciences sociales · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.
Indexed as
Case-Control StudiesChildChild Development Disorders, PervasiveCognitionCognition DisordersDNA Copy Number VariationsFemaleHumansIntellectual DisabilityMaleMutationNerve Tissue ProteinsNeuronsSynapsesNerve Tissue ProteinsSHANK2 protein, human
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