{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:11:16Z","timestamp":1790017876887,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701125"],"award-info":[{"award-number":["81701125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Angelman syndrome (AS) is a rare neurodevelopmental disorder and is characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. Although the maternal chromosomal region 15q11.2\u2010q13 deletion is the most common mechanism of AS, ~10% of individuals with AS are caused by the intragenic variants in the maternally inherited <jats:italic>UBE3A<\/jats:italic>, which encodes an E3 ubiquitin ligase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical diagnoses were based on detailed clinical findings. Trio\u2010based exome sequencing was performed on the proband and her parents to identify the underlying genetic variants. The candidate variants were confirmed by Sanger sequencing following PCR amplification. In silico analyses were conducted to predict the effect of the identified variant on the function of <jats:italic>UBE3A<\/jats:italic> protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel variant c.2029G&gt;C (p. Gly677Arg) in <jats:italic>UBE3A<\/jats:italic> as the most promising candidate. In silico analyses showed that p.Gly677Arg in the <jats:italic>UBE3A<\/jats:italic> affects a highly conserved residue. Her mother had the variant at this locus. Sanger sequencing results showed that II\u20102, II\u20105, II\u20107, IV\u20101, III\u20105, III\u20107, III\u20108, and III\u20109 have the variant c.2029G&gt;C, and all patients inherited maternally variant in <jats:italic>UBE3A<\/jats:italic>, while the offsprings of the male carrier were unaffected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a novel variant (c.2029G&gt;C) in the <jats:italic>UBE3A<\/jats:italic> in a Chinese family with multigenerational intellectual disability and developmental delay. Our findings expanded the genotypic spectrum of AS and provided important information for genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1883","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T13:08:46Z","timestamp":1646053726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel variant in <scp>UBE3A<\/scp> in a family with multigenerational intellectual disability and developmental delay"],"prefix":"10.1002","volume":"10","author":[{"given":"Xuechao","family":"Zhao","sequence":"first","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zheng","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Provincial Key Laboratory of Children's Genetics And Metabolic Diseases Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyue","family":"Mei","sequence":"additional","affiliation":[{"name":"Henan Provincial Key Laboratory of Children's Genetics And Metabolic Diseases Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-7638","authenticated-orcid":false,"given":"Xiangdong","family":"Kong","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528\u2010019\u201009931\u20103"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S57386"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30273"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000328837"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e3181ee408e"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.12.834"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200258"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100299\u20108"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.097857.109"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u201011\u201070"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.01.033"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22687"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201859"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3715005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201264"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320560224"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31074"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0045\u20109380(06)80036\u20108"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1234"}],"container-title":["Molecular Genetics &amp; 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