{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:14:23Z","timestamp":1780406063988,"version":"3.54.1"},"reference-count":6,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare autosomal recessive ciliopathy with significant involvement of the skeleton, ectoderm, retina, kidneys, liver, lungs, and occasionally the brain. Cranioectodermal dysplasia\u20102 (CED2) is caused by homozygous or compound heterozygous mutation in the WD repeat\u2010containing protein 35 (<jats:italic>WDR35<\/jats:italic>). However, the current understanding of the CED2 prenatal phenotype is limited. Here, we describe the fetus at 12 + 4\u00a0weeks gestation from a Chinese family with healthy parents. The fetus presented with lymphedema, omphalocele, hydrops fetalis, abnormal posturing, hypoplasia of the ulna, hypoplasia of the radius, femoral bowing, short femur, ductus venosus agenesis, ventricular septal defect, and atrial septal defect. To our knowledge, apart from lymphedema and hydrop fetalis, no other phenotypes of the fetus described in this study have been reported in the CED2 prenatal phenotype. Compound heterozygous variants (c.3155\u20101G&gt;A and c.215\u20108T&gt;G) in the <jats:italic>WDR35<\/jats:italic> were identified via trio\u2010based exome sequencing and confirmed pathogenicity through mRNA splicing analysis in vivo. Collectively, we clarified the genetic diagnosis for the fetus with multiple ultrasound abnormalities, which is helpful for genetic counseling and early prenatal diagnosis. Meanwhile, a definitive genetic diagnosis could aid in assessing the risk of recurrence during reproduction and support further pre\u2010implantation or prenatal diagnoses for the family. Additionally, the novel c.3155\u20101G&gt;A variant expands the spectrum of <jats:italic>WDR35<\/jats:italic> variants. The presence of omphaloceles, abnormal posturing, hypoplasia of the ulna, hypoplasia of the radius, femoral bowing, short femur, ductus venosus agenesis, ventricular septal defect, and atrial septal defect in fetus with <jats:italic>WDR35<\/jats:italic> variants may expand the prenatal phenotypic spectrum of CED2.<\/jats:p>","DOI":"10.1002\/pd.6821","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T09:19:14Z","timestamp":1748596754000},"page":"1053-1057","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aberrant Splicing Caused by Compound Heterozygous Variants in <i>WDR35<\/i> Identified in a Fetus With Cranioectodermal Dysplasia 2"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-1511","authenticated-orcid":false,"given":"Cong","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Medical Genetics \/ Prenatal Diagnostic Center West China Second University Hospital Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \/ Prenatal Diagnostic Center West China Second University Hospital Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \/ Prenatal Diagnostic Center West China Second University Hospital Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqun","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \/ Prenatal Diagnostic Center West China Second University Hospital Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ultrasonic Sichuan Provincial Woman's and Children's Hospital \/ The Affiliated Women's and Children's Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0975-375X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \/ Prenatal Diagnostic Center West China Second University Hospital Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2011.088864"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62067"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35608"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102021\u2010108013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.010"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6821","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T03:40:25Z","timestamp":1752291625000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":6,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/pd.6821"],"URL":"https:\/\/doi.org\/10.1002\/pd.6821","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"assertion":[{"value":"2025-01-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}