ArticleHuman molecular genetics2014
Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 3 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Epigenetic alterations in patients with anorexia nervosa-a systematic review.Molecular psychiatry · 2024Pooled it
- Epigenetics in eating disorders: a systematic review.Molecular psychiatry · 2019Pooled it
- Case-control meta-analysis of blood DNA methylation and autism spectrum disorder.Molecular autism · 2018Pooled it
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- The Future of Epigenetics: Emerging Technologies and Clinical Applications.ACS pharmacology & translational science · 2026Review
- HDAC Inhibition Reshapes Splicing of Synaptic Plasticity-Related Genes and Neural Network Dynamics.Cellular and molecular neurobiology · 2026Article
- The Convergence of Early-Life Stress and Autism Spectrum Disorder on the Epigenetics of Genes Key to the HPA Axis.Biology · 2025Review
- Comprehensive behavioral characterization and impaired hippocampal synaptic transmission in R1117X Shank3 mutant mice.Translational psychiatry · 2025Article
- Dysregulated RNA-binding proteins and alternative splicing: Emerging roles in autism spectrum disorder.Molecules and cells · 2025Review
- Genome-wide DNA methylation profiles in the raphe nuclei of patients with autism spectrum disorder.Psychiatry and clinical neurosciences · 2025Article
- Epigenetic modulation rescues neurodevelopmental deficits in Syngap1Aging cell · 2025Article
- SpliceTransformer predicts tissue-specific splicing linked to human diseases.Nature communications · 2024Article
- Behavioral regression in shank3Research square · 2024Article
- Neuron type-specific proteomics reveals distinct Shank3 proteoforms in iSPNs and dSPNs lead to striatal synaptopathy in Shank3BMolecular psychiatry · 2024Article
- DNA Methylation in Autism Spectrum Disorders: Biomarker or Pharmacological Target?Brain sciences · 2024Review
- Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.Cell reports · 2024Article
- Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism AssociatedbioRxiv : the preprint server for biology · 2024Article
- Intercontinental insights into autism spectrum disorder: a synthesis of environmental influences and DNA methylation.Environmental epigenetics · 2024Review
- Metabolic shift toward ketosis in asocial cavefish increases social-like affinity.BMC biology · 2023Article
- Differential DNA Methylation from Autistic Children Enriches Evidence for Genes Associated with ASD and New Candidate Genes.Brain sciences · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
The molecular basis for the majority of cases of autism spectrum disorders (ASD) remains unknown. We tested the hypothesis that ASD have an epigenetic cause by performing DNA methylation profiling of five CpG islands (CGI-1 to CGI-5) in the SHANK3 gene in postmortem brain tissues from 54 ASD patients and 43 controls. We found significantly increased overall DNA methylation (epimutation) in three intragenic CGIs (CGI-2, CGI-3 and CGI-4). The increased methylation was clustered in the CGI-2 and CGI-4 in ∼15% of ASD brain tissues. SHANK3 has an extensive array of mRNA splice variants resulting from combinations of five intragenic promoters and alternative splicing of coding exons. Altered expression and alternative splicing of SHANK3 isoforms were observed in brain tissues with increased methylation of SHANK3 CGIs in ASD brain tissues. A DNA methylation inhibitor modified the methylation of CGIs and altered the isoform-specific expression of SHANK3 in cultured cells. This study is the first to find altered methylation patterns in SHANK3 in ASD brain samples. Our finding provides evidence to support an alternative approach to investigating the molecular basis of ASD. The ability to alter the epigenetic modification and expression of SHANK3 by environmental factors suggests that SHANK3 may be a valuable biomarker for dissecting the role of gene and environment interaction in the etiology of ASD.
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Registered trials
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.