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Ca<jats:sup>2+<\/jats:sup> signaling is emerging as a potential node in the genetic architecture of the disorder. We previously reported decreased inositol trisphosphate (IP<jats:sub>3<\/jats:sub>)-mediated Ca<jats:sup>2+<\/jats:sup> release from the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism \u2013 fragile X and tuberous sclerosis types 1 and 2 syndromes. We now extend those findings to a cohort of subjects with sporadic ASD without any known mutations. We developed and applied a high throughput Fluorometric Imaging Plate Reader (FLIPR) assay to monitor agonist-evoked Ca<jats:sup>2+<\/jats:sup> signals in human primary skin fibroblasts. Our results indicate that IP<jats:sub>3<\/jats:sub> -mediated Ca<jats:sup>2+<\/jats:sup> release from the endoplasmic reticulum in response to activation of purinergic receptors is significantly depressed in subjects with sporadic as well as rare syndromic forms of ASD. We propose that deficits in IP<jats:sub>3<\/jats:sub>-mediated Ca<jats:sup>2+<\/jats:sup> signaling represent a convergent hub function shared across the spectrum of autistic disorders \u2013 whether caused by rare highly penetrant mutations or sporadic forms \u2013 and holds promise as a biomarker for diagnosis and novel drug discovery.<\/jats:p>","DOI":"10.1038\/srep40740","type":"journal-article","created":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T10:44:33Z","timestamp":1485945873000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder"],"prefix":"10.1038","volume":"7","author":[{"given":"Galina","family":"Schmunk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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