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This study sought to determine whether <jats:italic>mGluR<\/jats:italic> Copy Number Variants (CNV\u2019s) were overrepresented in children with syndromic ASD and if <jats:italic>mGluR<\/jats:italic> \u201csecond hit\u201d confers additional risk for ASD in 22q11.2 Deletion Syndrome (22q11DS). To determine whether <jats:italic>mGluR<\/jats:italic> network CNV\u2019S are enriched in syndromic ASD, we examined microarrays from children with ASD (n\u2009=\u2009539). Patient categorization (syndromic vs nonsyndromic) was done via blinded medical chart review in <jats:italic>mGluR<\/jats:italic> positive and randomly selected <jats:italic>mGluR<\/jats:italic> negative cases. 11.5% of ASD had <jats:italic>mGluR<\/jats:italic> CNV\u2019s vs. 3.2% in controls (p\u2009&lt;\u20090.001). Syndromic ASD was more prevalent in children with <jats:italic>mGluR<\/jats:italic> CNVs (74% vs 16%, p\u2009&lt;\u20090.001). A comparison cohort with 22q11DS (n\u2009=\u200925 with ASD, n\u2009=\u200950 without ASD), all haploinsufficient for mGluR network gene <jats:italic>RANBP1<\/jats:italic>, were evaluated for \u201csecond <jats:italic>mGluR<\/jats:italic> hits\u201d. 20% with 22q11.2DS\u2009+\u2009ASD had \u201csecond hits\u201d in <jats:italic>mGluR<\/jats:italic> network genes vs 2% in 22q11.2DS-ASD (p\u2009&lt;\u20090.014). We propose that altered <jats:italic>RANBP1<\/jats:italic> expression may provide a mechanistic link for several seemingly unrelated genetic and environmental forms of ASD.<\/jats:p>","DOI":"10.1038\/srep19372","type":"journal-article","created":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T12:05:58Z","timestamp":1453205158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Role of mGluR Copy Number Variation in Genetic and Environmental Forms of Syndromic Autism Spectrum Disorder"],"prefix":"10.1038","volume":"6","author":[{"given":"Tara L.","family":"Wenger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlly","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"McDonald-McGinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice E.","family":"Morrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly S.","family":"Emanuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,19]]},"reference":[{"key":"BFsrep19372_CR1","unstructured":"Baio, J. et al. 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