{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:47:05Z","timestamp":1792043225940,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Angelman syndrome is a neurodevelopmental disorder characterized by intellectual disability (ID), a distinctive gait pattern, abnormal behaviors, severe impairment in language development, and characteristic facial features. Most cases are caused by the absence of a maternal contribution to the imprinted region on chromosome 15q11\u2010q13. Here, we present the first reported case of a 3\u2010year\u2010old boy with an atypical phenotype of Angelman syndrome due to uniparental isodisomy with two recessive homozygous pathogenic variants: in\n                    <jats:italic>HERC2<\/jats:italic>\n                    and\n                    <jats:italic>AP3B2<\/jats:italic>\n                    . Known phenotypes related to\n                    <jats:italic>HERC2<\/jats:italic>\n                    and\n                    <jats:italic>AP3B2<\/jats:italic>\n                    include ID and early infantile epileptic encephalopathy, respectively. The patient had severe global developmental delay and profound ID and showed a happy demeanor, stereotypic laughter, and hand\u2010flapping movements, but also irritability. Craniofacial dysmorphic features, including brachycephaly, strabismus, wide ala nasi, short philtrum, wide open mouth, and slight hypopigmentation were seen. Progressive microcephaly was noted. Magnetic resonance imaging of the brain showed delayed myelination and cerebral atrophy. Trio whole exome sequencing and CGH\u2010SNP array analysis revealed paternal uniparental isodisomy of chromosome 15 and two coexisting recessive diseases resulting from homozygous\n                    <jats:italic>HERC2<\/jats:italic>\n                    and\n                    <jats:italic>AP3B2<\/jats:italic>\n                    pathogenic variants. The pathogenic variant in\n                    <jats:italic>HERC2<\/jats:italic>\n                    was inherited from his heterozygous\u2010carrier father, and the variant in\n                    <jats:italic>AP3B2<\/jats:italic>\n                    was de novo. We suppose that these unusual features were the combination of the effect of three concomitant disorders.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62371","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T07:37:03Z","timestamp":1622101023000},"page":"3092-3098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Blended phenotype of combination of\n                    <scp>\n                      <i>HERC2<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>AP3B2<\/i>\n                    <\/scp>\n                    deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-4754","authenticated-orcid":false,"given":"Kimiko","family":"Ueda","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saiseikai Suita Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuiko","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7993-1964","authenticated-orcid":false,"given":"Eriko","family":"Nishi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-9610","authenticated-orcid":false,"given":"Tadashi","family":"Kaname","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Tokyo Women's Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-656X","authenticated-orcid":false,"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka 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