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Background Williams syndrome (WS) is a neurodevelopmental disorder that has been attributed to heterozygous deletions in chromosome 7q11.23 and exhibits a variety of physical, cognitive, and behavioral features. However, the genetic basis of this phenotypic variability is unclear. In this study, we identified genetic clues underlying these complex phenotypes. Methods Neurobehavioral function was assessed in WS patients and healthy controls. Total RNA was extracted from peripheral blood and subjected to microarray analysis, RNA‐sequencing, and qRT‐PCR. Weighted gene co‐expression network analysis was performed to identify specific alterations related to intermediate disease phenotypes. To functionally interpret each WS‐related module, gene ontology and disease‐related gene enrichment were examined. We also investigated the micro (mi)RNA expression profiles and miRNA co‐expression networks to better explain the regulation of the transcriptome in WS. Results Our analysis identified four significant co‐expression modules related to intermediate WS phenotypes. Notably, the three upregulated WS‐related modules were composed exclusively of genes located outside the 7q11.23 region. They were significantly enriched in genes related to B‐cell activation, RNA processing, and RNA transport. BCL11A, which is known for its association with speech disorders and intellectual disabilities, was identified as one of the hub genes in the top WS‐related module. Finally, these key upregulated mRNA co‐expression modules appear to be inversely correlated with a specific downregulated WS‐related miRNA co‐expression module. Conclusions Dysregulation of the mRNA/miRNA network involving genes outside of the 7q11.23 region is likely related to the complex phenotypes observed in WS patients.

Increasing evidence suggests that epigenetic mechanisms play a role in the etiology of autism spectrum disorder (ASD). To date, several studies have attempted to identify epigenetic biomarkers for ASD. However, reliable markers remain to be established and most of these studies have focused on pediatric patients with ASD. In this study, we sought to find an epigenetic DNA methylation biomarker from peripheral blood for adult patients with high-functioning ASD. DNA methylation profiles were analyzed using the Illumina 450 K methylation array. To identify robust candidate markers, we employed two types of machine-learning algorithms for marker selection. We identified a potential marker (cg20793532) for which is the AUC value was 0.79. Notably, cg20793532 was annotated to the PPP2R2C gene, which was hypermethylated and down-regulated in blood from ASD patients compared to that in the controls. Although requiring careful interpretation, this pilot study seems to provide a potential blood biomarker for identifying individuals with high-functioning ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Owing to the difficulty of clinical diagnosis, ASD without intellectual disability (i.e., high-functioning ASD) is often overlooked. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. We identified miR-6126 as being robustly down-regulated in ASD and correlated with the severity of social deficits. Enrichment analysis of predicted target genes revealed potential association with neurons, synapses, and oxytocin signaling pathways. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.