{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T14:38:43Z","timestamp":1777473523426,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T00:00:00Z","timestamp":1466121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001673","name":"J\u00e9r\u00f4me Lejeune Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>We report a 25\u2010year\u2010old female confirmed to have Smith\u2013Magenis syndrome (SMS) due to a de novo <jats:italic>RAI1<\/jats:italic> variant. Her past history is significant for developmental and intellectual delay, early and escalating maladaptive behaviors, and features consistent with significant sleep disturbance, the etiology of which was not confirmed for over two decades. The diagnosis of SMS was initially suspected in 1998 (at age 12 years), but that was 5 years before the initial report of <jats:italic>RAI1<\/jats:italic> variants as causative of the SMS phenotype; cytogenetic fluorescence in situ hybridization studies failed to confirm an interstitial deletion of 17p11.2. Re\u2010evaluation for suspected SMS was pursued with <jats:italic>RAI1<\/jats:italic> sequencing analysis in response to urgent parental concerns of escalating behaviors and aggression with subsequent incarceration of the subject for assault of a health professional. Genetic analysis revealed a de novo <jats:italic>RAI1<\/jats:italic> (NM_030665.3) nonsense variant, c.5536C&gt;T; p.Q1846X. This case illustrates the importance of confirming the SMS diagnosis, which is associated with cognitive and functional impairment, as well as significant psychiatric co\u2010morbidities and behavioral problems. The diagnosis was particularly relevant to the legal discussion and determination of her competence to stand trial. As other similar cases may exist, this report will help to increase awareness of the possibility of a very late diagnosis of SMS, with the need for re\u2010evaluation of individuals suspected to have SMS who were initially evaluated prior to the identification of the <jats:italic>RAI1<\/jats:italic> gene. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37602","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T06:56:08Z","timestamp":1466146568000},"page":"2383-2388","source":"Crossref","is-referenced-by-count":7,"title":["Delayed diagnosis in a house of correction: Smith\u2013Magenis syndrome due to a de novo nonsense <i>RAI1<\/i> variant"],"prefix":"10.1002","volume":"170","author":[{"given":"Patra","family":"Yeetong","sequence":"first","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Faculty of Science Division of Human Genetics Department of Botany Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Vilboux","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Division of Medical Genomics Inova Translational Medicine Institute Falls Church Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Boulier","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda E.","family":"Schnur","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, Cooper University Health Care Cooper Medical School of Rowan University Camden New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Office of Clinical Director National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan","family":"Huizing","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Laje","sequence":"additional","affiliation":[{"name":"Washington Behavioral Medicine Associates, LLC, Autism Spectrum Partners, LLC Maryland Institute for Neuroscience and Development (MIND) Chevy Chase Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann C. 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