{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:24:57Z","timestamp":1783596297803,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402162"],"award-info":[{"award-number":["82402162"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301936"],"award-info":[{"award-number":["82301936"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Gynecology &amp; Obste"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the genetic etiology of fetal postural anomalies using whole\u2010exome sequencing (WES) and elucidate the genotype\u2013phenotype correlation between prenatal sonographic findings and molecular signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective single\u2010center cohort study was conducted at the Center of Medical Genetics, Hubei Maternal and Child Health Hospital between September 2020 and August 2025. The study enrolled 100 fetuses with prenatal ultrasound\u2010confirmed postural anomalies, including fixed abnormal hand positioning, persistent limb contractures, clubfeet, or lower\u2010limb deformities. All cases first underwent chromosomal microarray analysis (CMA) or copy\u2010number variation sequencing (CNV\u2010seq). WES was subsequently performed on fetuses with normal CMA\/ CNV\u2010seq results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 100 fetuses, 12 (12.0%, 95% confidence interval [CI]: 6.4%\u201320.0%) pathogenic chromosomal abnormalities were identified by CMA\/CNV\u2010seq. WES was performed on the remaining 88 fetuses, yielding a molecular diagnosis in 17 (19.3%, 95% CI: 11.7%\u201329.1%) cases. The combined sequential testing strategy (CMA\/CNV\u2010seq followed by WES) achieved an overall diagnostic yield of 29.0% (95% CI: 20.4%\u201338.9%). Notably, no monogenic pathogenic variants were identified in fetuses with truly isolated postural anomalies; the diagnostic yield was significantly higher in cases with additional limb or extra\u2010skeletal malformations. The 17 positive cases involved 26 distinct variants across 16 genes, with recurrent variants in\n                      <jats:italic>FGFR2<\/jats:italic>\n                      and\n                      <jats:italic>NEK1<\/jats:italic>\n                      (two cases each). While\n                      <jats:italic>SOX9<\/jats:italic>\n                      is frequently implicated in other cohorts, it was absent in our study; instead,\n                      <jats:italic>COL1A1<\/jats:italic>\n                      and\n                      <jats:italic>DYNC2H1<\/jats:italic>\n                      emerged as the most frequently shared genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WES provides a substantial incremental yield (19.3%, 95% CI: 11.7%\u201329.1%) in fetuses with negative results on CMA\/CNV\u2010seq. WES should be prioritized for fetuses with postural anomalies co\u2010occurring with extra\u2010skeletal defects, as isolated postural anomalies demonstrate a negligible monogenic risk. Our findings expand the genetic spectrum of fetal postural anomalies and inform precision genetic counseling and obstetric management, emphasizing phenotype\u2010driven testing algorithms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ijgo.71221","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:58:01Z","timestamp":1783594681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The added value of whole\u2010exome sequencing for fetuses with postural defects by prenatal ultrasound"],"prefix":"10.1002","author":[{"given":"Yayun","family":"Qin","sequence":"first","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqi","family":"Yi","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zeng","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-9037","authenticated-orcid":false,"given":"Jieping","family":"Song","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Maternal and Child Health Hospital of Hubei Province  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4724"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-018-0913-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2025.101690"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/bpo.0000000000001191"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4274\/tjod.galenos.2020.60669"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61721"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2020.105047"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2022.2128654"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13091573"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.70076"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-023-01733-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.160"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2476038"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106377"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)31940-8"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)32042-7"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6709"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6714"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.177"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-108040"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2017.04.007"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6115"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.24862"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01169-9"}],"container-title":["International Journal of Gynecology &amp; 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