Functional platelet studies and (epi)genetics to unravel the molecular basis of autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders of unknown etiology but with a heritability estimate exceeding 90%. Despite remarkable advances in genetic findings in the past few years, elucidating the etiology of ASD remains challenging because of the genetic variety, the heterogeneity of symptoms and most importantly, the difficulties in modeling the disease in vitro and in vivo due to the lack of easy accessible functional tests. Recently, these challenges have been mitigated by compelling evidence that platelet research can contribute to unravel disease mechanisms underlying neuropathology. Platelets share several biological features with neurosecretory cells, such as a common gene expression profile, similarities in receptor expression, granule composition and secretory machinery. Genetic defects that influence neuronal signaling can therefor likewise interfere with platelet function. Initial studies have indeed confirmed structural and secretion abnormalities in platelets from ASD patients with identified genetic defects in genes related to the pathways of granule trafficking and secretion. This project describes how we will advance these recent findings by combining functional and morphological platelet studies with (epi)genetic screenings of ASD patients, and by using state-of-the-art in vitro studies to elucidate the role of newly identified genes in relation to the dense granule secretion system.