{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:43:34Z","timestamp":1790073814211,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"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\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["FoUI\u2010961392"],"award-info":[{"award-number":["FoUI\u2010961392"]}],"id":[{"id":"10.13039\/501100004348","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;amp; Gyne"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the diagnostic yield of clinical whole\u2010genome sequencing (WGS) in prenatally diagnosed non\u2010immune hydrops fetalis (NIHF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a retrospective study of 23 fetuses with prenatally diagnosed NIHF, negative for trisomies and copy\u2010number variants, referred for analysis by WGS with an\n                      <jats:italic>in\u2010silico<\/jats:italic>\n                      panel of 281 genes associated with hydrops fetalis. Due to identification of a high proportion of causative variants in the\n                      <jats:italic>HRAS<\/jats:italic>\n                      gene in the main cohort, Sanger sequencing of\n                      <jats:italic>HRAS<\/jats:italic>\n                      was performed in a replication cohort, consisting of 24 additional fetuses with NIHF that were negative for trisomies and copy\u2010number variants and had not undergone WGS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 23 fetuses in the main cohort, a molecular diagnosis was achieved in 12 (52.2%). Pathogenic or likely pathogenic variants were identified in seven genes:\n                      <jats:italic>HRAS<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095),\n                      <jats:italic>RIT1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092),\n                      <jats:italic>FOXP3<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>GLB1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>MAP2K1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091),\n                      <jats:italic>PTPN11<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) and\n                      <jats:italic>RASA1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091). The inheritance pattern of the 12 causative variants was autosomal dominant in 10 cases (\n                      <jats:italic>HRAS, MAP2K1, PTPN11, RASA1, RIT1<\/jats:italic>\n                      ), autosomal recessive in one (\n                      <jats:italic>GLB1<\/jats:italic>\n                      ) and X\u2010linked recessive in one (\n                      <jats:italic>FOXP3<\/jats:italic>\n                      ). Of the 24 fetuses in the replication cohort, a pathogenic variant in\n                      <jats:italic>HRAS<\/jats:italic>\n                      was identified in one\n                      <jats:italic>,<\/jats:italic>\n                      resulting in an overall frequency of causative\n                      <jats:italic>HRAS<\/jats:italic>\n                      variants of 12.8% (6\/47) in our two cohorts.\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 52% with clinical WGS in NIHF using an\n                      <jats:italic>in\u2010silico<\/jats:italic>\n                      panel of 281 genes. However, the high diagnostic yield may be attributed to the small sample size and possible over\u2010representation of severe phenotypes in the included fetuses. Bearing in mind that chromosomal abnormalities were excluded in our cohorts, a detection rate of up to 75% is possible in prenatally diagnosed NIHF when WGS analysis includes calling of chromosomal aberrations. \u00a9 2022 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.24911","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T11:55:10Z","timestamp":1649505310000},"page":"487-493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Diagnostic yield using whole\u2010genome sequencing and\n                    <i>in\u2010silico<\/i>\n                    panel of 281 genes associated with non\u2010immune 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