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Background  The inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level.    Method  Here, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls.    Results  Copy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors  FOXO1  and  HAND2  in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes  EHPB2  and  RORA , both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons.    Conclusions  Finding a significant increase in both  HERC2  and  UBE3A  in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and  UBE3A  specific classes of AS mutation where  HERC2  is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes  EHPB2  and  RORA  indicating a possible connection between this syndromic form of ASD and idiopathic cases.    Electronic supplementary material  The online version of this article (10.1186/s13229-018-0191-y) contains supplementary material, which is available to authorized users.

Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons