{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:14:24Z","timestamp":1780596864569,"version":"3.54.1"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2018YFC1002206\u20102"],"award-info":[{"award-number":["2018YFC1002206\u20102"]}],"id":[{"id":"10.13039\/501100002855","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":[[2022,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the utility of trio\u2010based prenatal exome sequencing (pES), incorporating splice\u2010site and mitochondrial genome assessment, in the prenatal diagnosis of fetuses with ultrasound anomalies and normal copy\u2010number variant sequencing (CNV\u2010seq) results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a prospective study of 90 ongoing pregnancies with ultrasound anomalies that underwent trio\u2010based pES after receiving normal CNV\u2010seq results, from September 2020 to November 2021, in a single center in China. By using pES with a panel encompassing exome coding and splicing regions as well as mitochondrial genome for fetuses and parents, we identified the underlying genetic causes of fetal anomalies, incidental fetal findings and parental carrier status. Information on pregnancy outcome and the impact of pES findings on parental decision\u2010making was collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 90 pregnancies included, 28 (31.1%) received a diagnostic result that could explain the fetal ultrasound anomalies. The highest diagnostic yield was noted for brain abnormalities (3\/6 (50.0%)), followed by hydrops (4\/9 (44.4%)) and skeletal abnormalities (13\/34 (38.2%)). Collectively, 34 variants of 20 genes were detected in the 28 diagnosed cases, with 55.9% (19\/34) occurring\n                      <jats:italic>de novo<\/jats:italic>\n                      . Variants of uncertain significance (VUS) associated with fetal phenotypes were detected in six (6.7%) fetuses. Interestingly, fetal (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) and parental (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) incidental findings (IFs) were detected in seven (7.8%) cases. These included two fetuses carrying a\n                      <jats:italic>de\u2010novo<\/jats:italic>\n                      likely pathogenic (LP) variant of the\n                      <jats:italic>CIC<\/jats:italic>\n                      and\n                      <jats:italic>FBXO11<\/jats:italic>\n                      genes, respectively, associated with neurodevelopmental disorders, and one fetus with a LP variant in a mitochondrial gene. The remaining fetus presented with unilateral renal dysplasia and was incidentally found to carry a pathogenic\n                      <jats:italic>PKD1<\/jats:italic>\n                      gene variant resulting in adult\u2010onset polycystic kidney, which was later confirmed to be inherited from the mother. In addition, parental heterozygous variants associated with autosomal recessive diseases were detected in three families, including one with additional fetal diagnostic findings. Diagnostic results or fetal IFs contributed to parental decision\u2010making about termination of the pregnancy in 26 families (26\/72 (36.1%)), while negative pES results or identification of VUS encouraged 40 families (40\/72 (55.6%)) to continue their pregnancy, which ended in a live birth in all cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Trio\u2010based pES can provide additional genetic information for pregnancies with fetal ultrasound anomalies without a CNV\u2010seq diagnosis. The incidental findings and parental carrier status reported by trio\u2010based pES with splice\u2010site and mitochondrial genome analysis extend its clinical application, but careful genetic counseling is warranted. \u00a9 2022 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.24974","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T03:44:30Z","timestamp":1655783070000},"page":"780-792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Utility of trio\u2010based prenatal exome sequencing incorporating splice\u2010site and mitochondrial genome assessment in pregnancies with fetal ultrasound anomalies: prospective cohort 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