Genetic networks suggest Asperger’s Syndrome as a distinct subtype of Autism Spectrum Conditions

Abstract

AbstractBackgroundThe Diagnostic and Statistical Manual of Mental Disorders (DSM-V) issued new diagnostic criteria for autism spectrum conditions (ASC) which excluded cases of Asperger’s syndrome (AS) and pervasive developmental disorder not otherwise specified (PDD-NOS). This negatively affected the support received by those affected. In this study, we explored if AS can be considered a subtype of autism.MethodsWe explored if AS is considered a subtype of autism through gene network analysis. We analysed the GEO microarray data of 170 autism patients, then, used a weighted gene co-expression network (WGCNA) pipeline. We explored whether these modules share the same expression patterns across autism subtypes. The study had 170 patients grouped into three groups: AS, autism, and PDD-NOS.ResultsTwenty-one genetic modules were constructed for autism spectrum conditions. However, only AS had a significant downregulation in one of the modules. The module genes were significantly involved in the regulation of proteolysis, catabolic process, and NF-kappaB signalling. Pathway analysis showed the association of these genes with RIPK1-mediated necrosis and regulation of necroptotic cell death. Brain enrichment analysis showed a spatiotemporal distribution. There was significant gene enrichment in the prefrontal cortex during infancy and childhood then it changes in adulthood to be more abundant in the cingulum bundle, and corpus callosum.ConclusionsOur results suggest AS can be a distinct subtype of ASD, showing a similar gene expression pattern. Spatiotemporal distribution of the module genes in different brain regions explains the high functionality in individuals with AS.