{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:26:53Z","timestamp":1780507613456,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Roberts syndrome (RBS), also known as Roberts\u2010SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the <jats:italic>ESCO2<\/jats:italic> gene. Cardinal clinical manifestations are pre\u2010 and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic <jats:italic>ESCO2<\/jats:italic> variations and complex cerebrovascular diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6\u2009years old and died of cerebellar hemorrhage secondary to an aneurysm at 13\u2009years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the <jats:italic>ESCO2<\/jats:italic> gene (c.1220A&gt;T, p.H407L and c.1562delC, p.A521fs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We describe complex cerebrovascular diseases in Roberts syndrome caused by novel <jats:italic>ESCO2<\/jats:italic> biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2177","type":"journal-article","created":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T02:30:25Z","timestamp":1680316225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic <i>ESCO2<\/i> variations"],"prefix":"10.1002","volume":"11","author":[{"given":"Shuang","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3207-718X","authenticated-orcid":false,"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-8473","authenticated-orcid":false,"given":"Xin\u2010Liang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12151"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201066795\u2010z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010022\u201006057\u20100"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247\u2010020\u201004716\u2010y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31819fd897"},{"issue":"3","key":"e_1_2_11_7_1","first-page":"239","article-title":"Roberts syndrome: Phenotypic variation, cytogenetic definition and heterozygote detection","volume":"34","author":"Maserati E.","year":"1991","journal-title":"Annales de G\u00e9n\u00e9tique"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000006851"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2022.2048563"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009219"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000119341.59445.cf"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050313X221094077"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010021\u201002531\u2010y"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61826"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/498695"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.12.013"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470735"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.068395"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1548"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3171\/2011.8.PEDS11117"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010022\u201001161\u20108"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:09:32Z","timestamp":1692547772000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/mgg3.2177"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2177","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"assertion":[{"value":"2023-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2177"}}