Autism and Williams syndrome: dissimilar socio-cognitive profiles with similar patterns of abnormal gene expression in the blood

Abstract

Autism Spectrum Disorders (ASD) and Williams Syndrome (WS) are complex cognitive conditions exhibiting quite opposite features in the social domain: whereas people with ASD are mostly hyposocial, subjects with WS are usually reported as hypersocial. At the same time, ASD and WS share some common underlying behavioral and cognitive deficits. It is not clear, however, which genes account for the attested differences (and similarities) in the socio-cognitive domain. In this paper we adopted a comparative-molecular approach and looked for genes that might be differentially (or similarly) regulated in the blood of people with these conditions. We found a significant overlap between genes dysregulated in the blood of patients compared to neurotypical controls, with most of them being upregulated or, in some cases, downregulated. Still, genes with similar expression trends can exhibit quantitative differences between conditions, with most of them being more dysregulated in WS than in ASD. Differentially-expressed genes are involved in aspects of brain development and function (particularly, dendritogenesis) and are expressed in brain areas (particularly, the cerebellum, the thalamus and the striatum) of relevance for the ASD and the WS etiopathogenesis. Overall, these genes emerge as promising candidates for the similarities and differences between the ASD and the WS socio-cognitive profiles.

DNA methylation mediates a randomized controlled trial home-visiting intervention during pregnancy and the Bayley infant’s cognitive scores at 12 months of age

“…In terms of potential mediators, 5 out of 12 DMPs with a significant mediation effect (ACME and total effect) were mapped to genes involved in neuron functions and some associated to neurodevelopmental disorders: MYOM2 (cg08174789), RB1 (cg13389575), C10orf118 (cg05405872), STXBP6 (cg11734401), and TOR1AIP2 (cg07761912) . [37][38][39] C10orf118 and STXBP6 are involved with vesicle trafficking and signaling 40 and are associated with dendritic protein localization in neurons. 41 TOR1AIP1 encodes cofactors for the ATPase TorsinA, important to maintain developing neurons, during neuronal differentiation.…”