{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:23:19Z","timestamp":1778563399183,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T00:00:00Z","timestamp":1461024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>This paper examines how <jats:styled-content style=\"fixed-case\">COMT<jats:sup>158<\/jats:sup><\/jats:styled-content> genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social cognitive problems in 22q11.2 deletion syndrome (<jats:styled-content style=\"fixed-case\">22q11DS<\/jats:styled-content>). Severity of autistic spectrum symptoms of 45 participants with <jats:styled-content style=\"fixed-case\">22q11DS<\/jats:styled-content> was assessed using the Autism Diagnostic Interview Revised. Face and facial emotion recognition was evaluated using standardized computer\u2010based test\u2010paradigms. Associations with <jats:styled-content style=\"fixed-case\">COMT<jats:sup>158<\/jats:sup><\/jats:styled-content> genotypes and proline levels were examined. High proline levels and poor face recognition in individuals with the <jats:styled-content style=\"fixed-case\"><jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>MET<\/jats:italic><\/jats:sup><\/jats:styled-content> allele, and poor facial emotion recognition, explained almost 50% of the variance in severity of autism symptomatology in individuals with <jats:styled-content style=\"fixed-case\">22q11DS<\/jats:styled-content>. High proline levels and a decreased capacity to break down dopamine as a result of the <jats:styled-content style=\"fixed-case\">COMT<jats:sup>MET<\/jats:sup><\/jats:styled-content> variant are both relevant in the expression of the social phenotype in patients. This epistatic interaction effect between the <jats:styled-content style=\"fixed-case\">COMT<jats:sup>158<\/jats:sup><\/jats:styled-content> genotype and proline on the expression of social deficits in <jats:styled-content style=\"fixed-case\">22q11DS<\/jats:styled-content> shows how factors other than the direct effects of the deletion itself can modulate the penetrance of associated cognitive and behavioural outcomes. These findings are not only relevant to our insight into <jats:styled-content style=\"fixed-case\">22q11DS<\/jats:styled-content>, but also provide a model to better understand the phenomenon of variable penetrance in other pathogenic genetic variants.<\/jats:p>","DOI":"10.1111\/cge.12766","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T11:26:21Z","timestamp":1456485981000},"page":"420-427","source":"Crossref","is-referenced-by-count":16,"title":["The role of <scp>COMT<\/scp> and plasma proline in the variable penetrance of autistic spectrum symptoms in 22q11.2 deletion syndrome"],"prefix":"10.1111","volume":"90","author":[{"given":"E.","family":"Hidding","sequence":"first","affiliation":[{"name":"Department of Clinical Child and Adolescent Studies, Faculty of Social and Behavioural Sciences Leiden University  Leiden The 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