{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:55:29Z","timestamp":1770753329597,"version":"3.50.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C1005725"],"award-info":[{"award-number":["2021R1C1C1005725"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Schaaf\u2013Yang syndrome (SYS) is a rare genetic disorder caused by pathogenic variants in\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      , a paternally expressed and maternally imprinted gene on 15q11.2. Genetic diagnosis of SYS is challenging due to clinical features that overlap with those of other rare syndromic disorders and limited clinician awareness regarding the diagnosis of imprinting disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We present a neonate presenting with respiratory distress and joint contractures, diagnosed with SYS through comprehensive genetic testing. Whole\u2010exome sequencing identified a heterozygous\n                      <jats:italic>de novo<\/jats:italic>\n                      nonsense variant in\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      c.2092G&gt;T [p.(Gly698Ter)]. To confirm the paternal origin of this variant, methylation\u2010sensitive restriction enzyme digestion followed by long\u2010range PCR, nested PCR, and Sanger sequencing was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      c.2092G&gt;T was absent in both parents, indicating a\n                      <jats:italic>de novo<\/jats:italic>\n                      mutation. Methylation analysis confirmed that the variant resided on the paternal allele, establishing its pathogenicity. A proband diagnostic approach integrating sequence analysis, parental testing, and methylation assays effectively delineates\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      variants and their inheritance patterns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study underscores the importance of combining genomic sequencing with methylation assay to accurately diagnose SYS, especially for\n                      <jats:italic>de novo<\/jats:italic>\n                      variants. The proposed diagnostic workflow facilitates reliable identification of pathogenic\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      mutations and their parental origin, improving diagnostic precision in clinical settings. Further research is needed to elucidate the molecular mechanisms underlying\n                      <jats:italic>MAGEL2<\/jats:italic>\n                      \u2010related disorders and develop targeted therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.70152","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T05:47:32Z","timestamp":1766382452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a\n                    <i>De Novo MAGEL2<\/i>\n                    Pathogenic Variant in Schaaf\u2013Yang Syndrome and the Importance of Paternal Allele Confirmation"],"prefix":"10.1002","volume":"40","author":[{"given":"Youn\u2010Ji","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon Jeong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Center for Clinical Medicine, Samsung Biomedical Research Institute Samsung Medical Center  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jooyoung","family":"Cha","sequence":"additional","affiliation":[{"name":"Center for Clinical Medicine, Samsung Biomedical Research Institute Samsung Medical Center  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja\u2010Hyun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-588X","authenticated-orcid":false,"given":"Sung Eun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Life Science and Biotechnology Yonsei University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine Chung\u2010Ang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-5236","authenticated-orcid":false,"given":"Mi\u2010Ae","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40650"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.53"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2776"},{"key":"e_1_2_13_5_1","volume-title":"GeneReviews","author":"Schaaf C. 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