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Trio whole\u2010exome sequencing (trio\u2010WES) was performed on the fetus and his parents to identify the underlying genetic cause. Candidate variants were validated by Sanger sequencing, and their molecular effects were analyzed through minigene assays. Trio\u2010WES identified a novel heterozygous variant (c.1977+1G&gt;C) in\n                    <jats:italic>FGFR1<\/jats:italic>\n                    , which is consistent with\n                    <jats:italic>FGFR1<\/jats:italic>\n                    \u2010related Hartsfield syndrome (HS; OMIM#615465). Sanger sequencing confirmed that this variant was de novo. The minigene assay revealed that all variants (c.1977+1G&gt;C, c.1977+1G&gt;A, and c.1977+1G&gt;T) at the splice site generated two aberrant splicing events: (1) complete retention of intron 14, leading to a frameshift and premature termination codon; and (2) skipping of exon 14, causing an in\u2010frame deletion of 41 amino acids. These events collectively impaired the function of the FGFR1 protein's tyrosine kinase domain. To our knowledge, prenatal reports of\n                    <jats:italic>FGFR1<\/jats:italic>\n                    \u2010related HS remain extremely limited, and this is the first molecularly confirmed prenatal diagnosis of HS in China. The findings not only expand the mutational spectrum of HS but also provide genetic counseling and reproductive guidance for this family.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64226","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T12:21:07Z","timestamp":1755087667000},"page":"59-66","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Diagnosis of Hartsfield Syndrome in the Fetus With Isolated Ectrodactyly Caused by a Novel Variant in\n                    <scp>\n                      <i>FGFR1<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8694-1705","authenticated-orcid":false,"given":"Jun","family":"An","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"},{"name":"Department of Obstetrics and Gynecology The Second People's Hospital of Changzhou (The Third Affiliated Hospital of Nanjing Medical University)  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2183-7890","authenticated-orcid":false,"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Department of Prenatal Diagnosis Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital)  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61354"},{"key":"e_1_2_11_3_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Dhamija 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