{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:30:11Z","timestamp":1787499011418,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011727","name":"Stockholm l\u00e4ns landsting","doi-asserted-by":"publisher","award":["FoUI\u2010961392"],"award-info":[{"award-number":["FoUI\u2010961392"]}],"id":[{"id":"10.13039\/501100011727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011727","name":"Stockholm l\u00e4ns landsting","doi-asserted-by":"publisher","award":["FoUI\u2010961849"],"award-info":[{"award-number":["FoUI\u2010961849"]}],"id":[{"id":"10.13039\/501100011727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"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>Objective<\/jats:title>\n                    <jats:p>To investigate the diagnostic yield of trio whole\u2010genome sequencing (WGS) in fetuses with various congenital malformations referred to a tertiary center for prenatal diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective study, 50 pregnancies with different congenital malformations, negative for trisomies and causative copy\u2010number variants, were analyzed further with fetal\u2013parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations on prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation or multiple pregnancy were excluded. WGS with the Illumina Inc. 30\u00d7 polymerase\u2010chain\u2010reaction\u2010free short\u2010read sequencing included analysis of single\u2010nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy\u2010number identification of\n                      <jats:italic>SMN1<\/jats:italic>\n                      and\n                      <jats:italic>SMN2<\/jats:italic>\n                      genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A molecular diagnosis was achieved in 13\/50 (26%) cases. Causative sequence variants were identified in 12 genes:\n                      <jats:italic>FGFR3<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092),\n                      <jats:italic>ACTA1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>CDH2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>COL1A2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>DHCR7<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>EYA1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>FBXO11<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>FRAS1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>L1CAM<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>OFD1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>PDHA1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) and\n                      <jats:italic>SOX9<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091). The phenotypes of the cases were divided into different groups, with the following diagnostic yields: skeletal malformation (4\/9 (44%)), multisystem malformation (3\/7 (43%)), central nervous system malformation (5\/15 (33%)) and thoracic malformation (1\/10 (10%)). Additionally, two cases carried variants that were considered potentially clinically relevant, even though they were assessed as variants of uncertain significance, according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15\/50 (30%) cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. This study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosomal aberrations were excluded from our cohort before WGS. As chromosomal aberrations are a well\u2010known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosomal aberrations, may show that the detection rate exceeds the diagnostic yield of this study. WGS can  add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition, as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choice for future pregnancies. \u00a9 2024 The Authors.\n                      <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.27592","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T02:03:47Z","timestamp":1706148227000},"page":"658-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Whole\u2010genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical 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