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The disease spectrum is broad, and only a limited number of prenatal cases have been reported to date. We report two well\u2010documented prenatal cases of\n                    <jats:italic>CAKUTHED<\/jats:italic>\n                    presenting with cardiovascular defects as the initial manifestation in the second trimester. Trio exome sequencing identified two\n                    <jats:italic>de novo<\/jats:italic>\n                    variants in\n                    <jats:italic>PBX1<\/jats:italic>\n                    (c.192\u20103C&gt;A and c.869G&gt;A), confirming the genetic diagnosis of\n                    <jats:italic>CAKUTHED<\/jats:italic>\n                    in the two fetuses. In Case 1, minigene assays validated that the c.192\u20103C&gt;A variant interfered with RNA splicing. The individual predominantly manifested tetralogy of Fallot and renal hypoplasia. In Case 2, the c.869G&gt;A missense variant was identified, with more complex clinical features. Cardiac malformations included coarctation of the aorta, pulmonary artery stenosis, coronary sinus dilatation, and persistent left superior vena cava. Moreover, the fetus exhibited severe growth restriction, polyhydramnios, and marked thoracic and pulmonary defects, with no significant structural abnormalities of the urinary system detected. Both pregnancies were subsequently terminated. Our report, by detailing the previously rarely reported prenatal clinical features and novel genetic variants, helps to expand the known phenotypic and genotypic spectrum of\n                    <jats:italic>PBX1<\/jats:italic>\n                    \u2010related disorders.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70148","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T10:17:38Z","timestamp":1775211458000},"page":"1909-1916","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular Defects as the Initial Presentation in Two Prenatal Cases of\n                    <scp>\n                      <i>De Novo<\/i>\n                    <\/scp>\n                    Heterozygous\n                    <scp>\n                      <i>PBX1<\/i>\n                    <\/scp>\n                    Variants"],"prefix":"10.1002","volume":"200","author":[{"given":"Zhu","family":"Lan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics 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":"Bocheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics 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":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-7991","authenticated-orcid":false,"given":"Shanling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics 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":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics 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 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