ArticleJournal of medical genetics2009
Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number.
Article in Journal of medical genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 200 citations in OpenAlex.
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Psychiatric illness and intellectual disability in the Prader-Willi syndrome with different molecular defects--a meta analysis.PloS one · 2013Pooled it
- Trial
- Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication.Research square · 2026Article
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus.International journal of molecular sciences · 2023Article
- Evidence for parent-of-origin effects in autism spectrum disorder: a narrative review.Journal of applied genetics · 2023Review
- Molecular and behavioral consequences of Ube3a gene overdosage in mice.JCI insight · 2022Article
- The Human-Restricted Isoform of the α7 nAChR, CHRFAM7A: A Double-Edged Sword in Neurological and Inflammatory Disorders.International journal of molecular sciences · 2022Review
- GABAIUPHAR/BPS guide to pharmacology CITE · 2021Article
- A case of 15q11-q13 duplication syndrome and literature review.Brain and behavior · 2021Review
- Hereditary Spastic Paraplegia and Intellectual Disability: Clinicogenetic Lessons From a Family Suggesting a Dual Genetics Diagnosis.Frontiers in neurology · 2020Article
- Possible Phenotypic Consequences of Structural Differences in Idic(15) in a Small Cohort of Patients.International journal of molecular sciences · 2019Article
- Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.Nature neuroscience · 2019Article
- DNA Methylation and Susceptibility to Autism Spectrum Disorder.Annual review of medicine · 2019Review
- Tissue Specific Reference Genes for MicroRNA Expression Analysis in a Mouse Model of Peripheral Nerve Injury.Frontiers in molecular neuroscience · 2019Article
- Rhythms of life: circadian disruption and brain disorders across the lifespan.Nature reviews. Neuroscience · 2019Review
- Epigenetics and cerebral organoids: promising directions in autism spectrum disorders.Translational psychiatry · 2018Review
- Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons.Molecular autism · 2018Article
- Glial overexpression of Dube3a causes seizures and synaptic impairments in Drosophila concomitant with down regulation of the NaNeurobiology of disease · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundChromosome 15q11-13 contains a cluster of imprinted genes essential for normal mammalian neurodevelopment. Deficiencies in paternal or maternal 15q11-13 alleles result in Prader-Willi or Angelman syndromes, respectively, and maternal duplications lead to a distinct condition that often includes autism. Overexpression of maternally expressed imprinted genes is predicted to cause 15q11-13-associated autism, but a link between gene dosage and expression has not been experimentally determined in brain.
methodsPostmortem brain tissue was obtained from a male with 15q11-13 hexasomy and a female with 15q11-13 tetrasomy. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure 10 15q11-13 transcripts in maternal 15q11-13 duplication, Prader-Willi syndrome, and control brain samples. Southern blot, bisulfite sequencing and fluorescence in situ hybridisation were used to investigate epigenetic mechanisms of gene regulation.
resultsGene expression and DNA methylation correlated with parental gene dosage in the male 15q11-13 duplication sample with severe cognitive impairment and seizures. Strikingly, the female with autism and milder Prader-Willi-like characteristics demonstrated unexpected deficiencies in the paternally expressed transcripts SNRPN, NDN, HBII85, and HBII52 and unchanged levels of maternally expressed UBE3A compared to controls. Paternal expression abnormalities in the female duplication sample were consistent with elevated DNA methylation of the 15q11-13 imprinting control region (ICR). Expression of non-imprinted 15q11-13 GABA receptor subunit genes was significantly reduced specifically in the female 15q11-13 duplication brain without detectable GABRB3 methylation differences.
conclusionOur findings suggest that genetic copy number changes combined with additional genetic or environmental influences on epigenetic mechanisms impact outcome and clinical heterogeneity of 15q11-13 duplication syndromes.
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Registered trials
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