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Of particular interest is the unusual social\u2010cognitive profile evidenced by deficits in social cognition and communication reminiscent of autism spectrum disorders (<jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>) that are juxtaposed with normal or even relatively enhanced social motivation. Interestingly, duplications in the same region also result in <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>\u2010like phenotypes as well as social phobias. Thus, the region clearly regulates human social motivation and behavior, yet the relevant gene(s) have not been definitively identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Here, we deeply phenotyped 85 individuals with <jats:styled-content style=\"fixed-case\">WS<\/jats:styled-content> and used exome sequencing to analyze common and rare variation for association with the remaining variance in social behavior as assessed by the Social Responsiveness Scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We replicated the previously reported unusual juxtaposition of behavioral symptoms in this new patient collection, but we did not find any new alleles of large effect in the targeted analysis of the remaining copy of genes in the Williams syndrome critical region. However, we report on two nominally significant <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in two genes that have been implicated in the cognitive and social phenotypes of Williams syndrome, <jats:italic><jats:styled-content style=\"fixed-case\">BAZ<\/jats:styled-content>1B<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">GTF<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">IRD<\/jats:styled-content>1<\/jats:italic>. Secondary discovery driven explorations focusing on known <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content> genes and an exome wide scan do not highlight any variants of a large effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Whole exome sequencing of 85 individuals with <jats:styled-content style=\"fixed-case\">WS<\/jats:styled-content> did not support the hypothesis that there are variants of large effect within the remaining Williams syndrome critical region that contribute to the social phenotype. This deeply phenotyped and genotyped patient cohort with a defined mutation provides the opportunity for similar analyses focusing on noncoding variation and\/or other phenotypic domains.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.429","type":"journal-article","created":{"date-parts":[[2018,7,15]],"date-time":"2018-07-15T23:23:40Z","timestamp":1531697020000},"page":"749-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exome sequencing of 85 Williams\u2013Beuren syndrome cases rules out coding variation as a major contributor to remaining variance in social behavior"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0858-3242","authenticated-orcid":false,"given":"Nathan D.","family":"Kopp","sequence":"first","affiliation":[{"name":"Department of Genetics Washington University School of Medicine St. Louis Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phoebe C. 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