{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:01:25Z","timestamp":1791356485223,"version":"4.3.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,7,31]],"date-time":"2003-07-31T00:00:00Z","timestamp":1059609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Angelman syndrome (AS) is an imprinted neurobehavioral disorder characterized by mental retardation, absent speech, excessive laughter, seizures, ataxia, and a characteristic EEG pattern. Classical lesions, including deletion, paternal disomy, or epigenetic mutation, are confirmatory of AS diagnoses in 80% of cases. Loss\u2010of\u2010function mutations of the <jats:italic>UBE3A<\/jats:italic> gene have been identified in \u223c8% of AS cases, failing to account for the remaining patient population, and there appears to be a higher prevalence of mutations in familial than sporadic cases. We screened <jats:italic>UBE3A<\/jats:italic> in 45 index cases of AS without obvious 15q11\u201013 abnormalities. Pathological mutations were identified in 3\/6 (50%) familial and 4\/39 (&gt;10%) sporadic cases. By combining our data with those of the literature, we demonstrate statistically that the frequency of <jats:italic>UBE3A<\/jats:italic> mutations is significantly higher in the familial than sporadic subsets of AS. This indicates that an independent molecular mechanism or \u2018phenocopy\u2019 exists for the sporadic group. Rett syndrome (RS), caused by mutations of the <jats:italic>MECP2<\/jats:italic> gene, and patients with deletions of 22q13.3\u2009\u2192\u2009qter, have overlapping clinical features with AS. We screened 24 of the sporadic AS cases without detectable <jats:italic>UBE3A<\/jats:italic> mutations for mutations of <jats:italic>MECP2<\/jats:italic>, but found none. A separate cohort of 43 atypical patients with features common to AS and RS, in whom 15q11\u201013 lesions and 22q13.3\u2009\u2192\u2009qter deletion had been ruled out, were also screened for <jats:italic>MECP2<\/jats:italic> mutations. One male patient was mosaic for a frameshift mutation of this gene (previously reported). While <jats:italic>MECP2<\/jats:italic> mutations can cause a phenotype reminiscent of AS in rare cases, they fail to account for the excess of sporadic patients with a definitive clinical diagnosis of AS. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.20343","type":"journal-article","created":{"date-parts":[[2004,2,18]],"date-time":"2004-02-18T17:13:54Z","timestamp":1077124434000},"page":"167-172","source":"Crossref","is-referenced-by-count":27,"title":["Investigation of <i>UBE3A<\/i> and <i>MECP2<\/i> in Angelman syndrome (AS) and patients with features of AS"],"prefix":"10.1002","volume":"125A","author":[{"given":"Megan P.","family":"Hitchins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rickard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Dhalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert B.A.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Winter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus 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