{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:44:35Z","timestamp":1790603075895,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Non\u2010immune hydrops fetalis (NIHF) is a spectrum of disease involving heterogeneous etiologies. Prenatal application of whole exome sequencing (WES) has emerged as a valuable tool to decipher genetic causes in structural abnormalities detected by fetal ultrasound. Here, we reviewed index cases of NIHF whose genetic etiologies were delineated by WES.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective study on our pilot series (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) of NIHF that underwent WES with outcomes systematically reviewed. For each case, we performed a detailed sonographic examination for anasarca, virology profile, karyotyping, and chromosomal microarray analysis (CMA), in addition to WES performed either prenatally or postnatally.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between December 2019 and July 2024, 12 fetuses with abnormal fluid accumulation in fetal compartments, despite normal karyotyping and CMA, underwent WES to elucidate potential genetic etiologies. Variant interpretation was performed in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). A definitive molecular diagnosis was established in all 12 cases, with identified disorders including lymphatic abnormalities (33%), musculoskeletal disorders (30%), and syndromic conditions (17%). All recurrent cases (3\/3, 100%) and those who received fetal therapy (4\/4, 100%) have a definite molecular diagnosis. Two survived fetuses were diagnosed in the first and third trimesters, respectively, while four infants died and six couples decided to terminate the pregnancy due to disease progression. Two novel founder variants (\n                      <jats:italic>HSPG2<\/jats:italic>\n                      and\n                      <jats:italic>BBS2<\/jats:italic>\n                      ) were found.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WES is an effective tool to determine the genetic diagnosis of NIHF cases and would discover more novel causative genes to match the prenatal phenotypes exhibited.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jog.70039","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T02:41:27Z","timestamp":1754966487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic etiologies associated with non\u2010immune hydrops fetalis delineated by whole exome sequencing: A pilot series and its implications in prenatal genetic counseling"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-2158","authenticated-orcid":false,"given":"Zhu Wei","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwo\u2010Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology Central Taiwan University of Science and Technology  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Bioscience Technology Chung Yuan Christian University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Genomic Medicine and Center for Medical Genetics Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei\u2010Hui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Genomic Medicine and Center for Medical Genetics Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Medical Genetics National Taiwan University Hospital  Taipei Taiwan"},{"name":"Department of Obstetrics and Gynecology, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Post\u2010Baccalaureate Medicine, College of Medicine National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2023643"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.12.018"},{"key":"e_1_2_9_4_1","volume-title":"Fetology: diagnosis and management of the fetal patient, 2e","author":"Bianchi DW","year":"2015"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.23652"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2017-0124"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641950903323244"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.07.016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jum.14462"},{"key":"e_1_2_9_10_1","volume-title":"The care of women requesting induced abortion","author":"The Royal College of Obstetricians and Gynaecologists","year":"2011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.23119"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.26114"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.616392"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.27501"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1631-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.41"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.24911"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2016.09.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.09.039"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.27618"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.010"}],"container-title":["Journal of Obstetrics and Gynaecology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jog.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T01:39:18Z","timestamp":1763602758000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/jog.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/jog.70039"],"URL":"https:\/\/doi.org\/10.1111\/jog.70039","archive":["Portico"],"relation":{},"ISSN":["1341-8076","1447-0756"],"issn-type":[{"value":"1341-8076","type":"print"},{"value":"1447-0756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70039"}}