Angelman Syndrome and Angelman-like Syndromes Share the Same Calcium-Related Gene Signatures

Int J Mol Sci. 2021 Sep 13;22(18):9870. doi: 10.3390/ijms22189870.


Angelman-like syndromes are a group of neurodevelopmental disorders that entail clinical presentation similar to Angelman Syndrome (AS). In our previous study, we showed that calcium signaling is disrupted in AS, and we identified calcium-target and calcium-regulating gene signatures that are able to differentiate between AS and their controls in different models. In the herein study, we evaluated these sets of calcium-target and calcium-regulating genes as signatures of AS-like and non-AS-like syndromes. We collected a number of RNA-seq datasets of various AS-like and non-AS-like syndromes and performed Principle Component Analysis (PCA) separately on the two sets of signature genes to visualize the distribution of samples on the PC1-PC2 plane. In addition to the evaluation of calcium signature genes, we performed differential gene expression analyses to identify calcium-related genes dysregulated in each of the studied syndromes. These analyses showed that the calcium-target and calcium-regulating signatures differentiate well between AS-like syndromes and their controls. However, in spite of the fact that many of the non-AS-like syndromes have multiple differentially expressed calcium-related genes, the calcium signatures were not efficient classifiers for non-AS-like neurodevelopmental disorders. These results show that features based on clinical presentation are reflected in signatures derived from bioinformatics analyses and suggest the use of bioinformatics as a tool for classification.

Keywords: Angelman syndrome; Angelman-like syndromes; RNA sequencing; calcium signaling; calcium-regulating genes; calcium-target genes; transcriptome.

MeSH terms

  • Angelman Syndrome / genetics*
  • Angelman Syndrome / pathology
  • Calcium / metabolism
  • Calcium Signaling / genetics*
  • Chromosome Deletion
  • Computational Biology*
  • Gene Expression Regulation / genetics
  • Humans
  • Principal Component Analysis
  • RNA-Seq


  • Calcium