{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:24:40Z","timestamp":1773278680899,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"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                    Silver\u2013Russell syndrome (SRS) is a rare genetic condition primarily characterized by growth restriction and facial dysmorphisms. While hypomethylation of\n                    <jats:italic>H19\/IGF2<\/jats:italic>\n                    :IG\u2010DMR (imprinting control region 1 [IC1]) located at 11p15.5 and maternal uniparental disomy of chromosome 7 (upd[7]mat) are the most common genetic mechanisms responsible for SRS, the expanding body of literature describing alternative causative variants suggests SRS is a highly heterogeneous condition, also involving variation in the\n                    <jats:italic>HMGA2\u2010PLAG1\u2010IGF2<\/jats:italic>\n                    pathway. We report a familial\n                    <jats:italic>PLAG1<\/jats:italic>\n                    deletion in association with a complex chromosomal rearrangement. We describe two siblings with differing unbalanced chromosomal rearrangements inherited from a mother with a 5\u2010breakpoint balanced complex rearrangement involving chromosomes 2, 8, and 21. The overlapping but diverse phenotypes in the siblings were characterized by shared SRS\u2010like features, underlined by a\n                    <jats:italic>PLAG1<\/jats:italic>\n                    whole gene deletion. Genetic analysis and interpretation was further complicated by a meiotic recombination event occurring in one of the siblings. This family adds to the limited literature available on\n                    <jats:italic>PLAG1<\/jats:italic>\n                    \u2010related SRS. We have reviewed all currently known cases aiming to define the associated phenotype and guide future genetic testing strategies. The heterogeneity of SRS is further expanded by the involvement of complex cytogenomic abnormalities, imposing requirements for a comprehensive approach to testing and genetic counseling.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62391","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T08:16:27Z","timestamp":1625472987000},"page":"3136-3145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Further heterogeneity in\n                    <scp>Silver\u2013Russell<\/scp>\n                    syndrome:\n                    <scp>\n                      <i>PLAG1<\/i>\n                    <\/scp>\n                    deletion in association with a complex chromosomal rearrangement"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7460-1576","authenticated-orcid":false,"given":"Rebecca E.","family":"Brereton","sequence":"first","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen J.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"},{"name":"Pathology and Laboratory Medicine, Medical School The University of Western Australia Faculty of Health and Medical Sciences  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soruba","family":"Sivamoorthy","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Ramos Vasques Walters","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicki","family":"Chabros","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Marchin","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Grumball","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmara","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Uzaraga","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Peverall","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Arscott","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Beilby","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"},{"name":"Pathology and Laboratory Medicine, Medical School The University of Western Australia Faculty of Health and Medical Sciences  Perth Western Australia Australia"},{"name":"The University of Western Australia School of Biomedical Sciences  Nedlands Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine S.","family":"Choong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Perth Children's Hospital  Nedlands Western Australia Australia"},{"name":"Paediatrics, Medical School, Faculty of Health and Medical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharron","family":"Townshend","sequence":"additional","affiliation":[{"name":"Genetic Services of Western Australia, King Edward Memorial Hospital  Subiaco Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitar N.","family":"Azmanov","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics, PathWest Laboratory Medicine QEII Medical Centre  Nedlands Western Australia Australia"},{"name":"Pathology and Laboratory Medicine, Medical School The University of Western Australia Faculty of Health and Medical Sciences  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.105"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102979"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320530311"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1897"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35699"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.29"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01419.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35658"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-020-00865-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.04.027"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35220"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01683-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmr010"},{"key":"e_1_2_9_15_1","unstructured":"Saal H. M. Harbison M. D. &Netchine I.(2019).Silver\u2010Russell syndrome.GeneReviews."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7438"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-93"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121461"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.079111"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.138"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62391","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:54:24Z","timestamp":1773226464000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/ajmg.a.62391"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62391","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"assertion":[{"value":"2021-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}