{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:11:47Z","timestamp":1793059907996,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The identification of structural variants and single\u2010nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole\u2010genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed trio WGS with a minimum coverage of 40\u00d7 on the MGI DNBSEQ\u2010T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2\/17). Both were exon\u2010level copy\u2010number variants of small size (3.03\u2009kb and 5.16\u2009kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of\n                      <jats:italic>FGF8<\/jats:italic>\n                      with holoprosencephaly and facial deformities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of\n                      <jats:italic>BBS9<\/jats:italic>\n                      and\n                      <jats:italic>FGF8<\/jats:italic>\n                      . \u00a9 2023 International Society of Ultrasound in Obstetrics and Gynecology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.27517","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:24:18Z","timestamp":1697437458000},"page":"664-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Whole\u2010genome sequencing analysis in fetal structural anomalies: novel phenotype\u2013genotype discoveries"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-982X","authenticated-orcid":false,"given":"Q.","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Key Technology of Birth Defect Control and Prevention Screening and Diagnostic R&amp;D Center  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bai","sequence":"additional","affiliation":[{"name":"Becreative Lab Co. Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Lou","sequence":"additional","affiliation":[{"name":"Becreative Lab Co. Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Sun","sequence":"additional","affiliation":[{"name":"Biosan Biochemical Technologies Co. Ltd.  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Lian","sequence":"additional","affiliation":[{"name":"Biosan Biochemical Technologies Co. Ltd.  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Center, Peking Union Medical College Hospital Peking Union Medical College &amp; Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-3239"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9485-8_20"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-395269"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0639-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203382"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31940-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32042-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00139-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0675-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00761"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5195"},{"issue":"302","key":"e_1_2_8_13_1","article-title":"Whole genome sequencing vs chromosomal microarray analysis in prenatal diagnosis","volume":"229","author":"Hu P","year":"2023","journal-title":"Am J Obstet Gynecol"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12030376"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.27491"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/318794"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13500"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0176"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200745"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6115"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0791-8"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-018-0053-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-022-00301-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0137-z"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0864-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004041"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03202-9"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121397"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312713"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.209213"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066494"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02324"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.00994.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607956104"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34538"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0454"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.08.178"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31623"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000302285"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1086\/344412"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2022.10.001"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.795194"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23038"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6146"}],"container-title":["Ultrasound in Obstetrics &amp; Gynecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.27517","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/uog.27517","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.27517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:37:57Z","timestamp":1786631877000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/uog.27517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/uog.27517"],"URL":"https:\/\/doi.org\/10.1002\/uog.27517","archive":["Portico"],"relation":{},"ISSN":["0960-7692","1469-0705"],"issn-type":[{"value":"0960-7692","type":"print"},{"value":"1469-0705","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,15]]},"assertion":[{"value":"2023-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}