{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:17:39Z","timestamp":1790457459709,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Conventional genetic tests (quantitative fluorescent\u2010PCR [QF\u2010PCR] and single nucleotide polymorphism\u2010array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first\u2010degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We established a genetic rES\u2010based diagnosis in 8 out of 23 fetuses (35%) without QF\u2010PCR or array abnormalities. Diagnoses included MIRAGE (\n                      <jats:italic>SAMD9<\/jats:italic>\n                      ), Zellweger (\n                      <jats:italic>PEX1<\/jats:italic>\n                      ), Walker\u2010Warburg (\n                      <jats:italic>POMGNT1<\/jats:italic>\n                      ), Noonan (\n                      <jats:italic>PTNP11<\/jats:italic>\n                      ), Kabuki\n                      <jats:italic>(KMT2D<\/jats:italic>\n                      ), and CHARGE (\n                      <jats:italic>CHD7<\/jats:italic>\n                      ) syndrome and two cases of Osteogenesis Imperfecta type 2 (\n                      <jats:italic>COL1A1<\/jats:italic>\n                      ). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8\u201020) days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.5781","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T07:29:37Z","timestamp":1594020577000},"page":"1300-1309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-2374","authenticated-orcid":false,"given":"Nicole","family":"Corsten\u2010Janssen","sequence":"first","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelijne","family":"Bouman","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janouk C. D.","family":"Diphoorn","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen J.","family":"Scheper","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne","family":"Kinds","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"el Mecky","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"},{"name":"Clinical Ethics and Law University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Breet","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke B. G. M.","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Suijkerbuijk","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4089-9973","authenticated-orcid":false,"given":"Leonie K.","family":"Duin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Prenatal Diagnosis University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn T. R.","family":"Manten","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Isala  Zwolle The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"van Langen","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf H.","family":"Sijmons","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Sikkema\u2010Raddatz","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Westers","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleo C.","family":"van Diemen","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,20]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Eurocat update: short report congenital anomalies Northern Netherlands 1981\u20132017 (update);2019.www.eurocat.umcg.nl"},{"key":"e_1_2_9_3_1","volume-title":"Impact of the 20\u2010week scan","author":"Fleurke\u2010Rozema JH","year":"2017"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-018-0409-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5195"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5114"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-2854"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302575110"},{"key":"e_1_2_9_10_1","unstructured":"Johns Hopkins University. 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