{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:50:06Z","timestamp":1747151406775,"version":"3.40.5"},"reference-count":5,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"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":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Exome sequencing in prenatal context confronts with pathogenic variants associated with phenotypes that are not detectable prenatally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A consanguineous couple was referred at 24 weeks of gestation for prenatal genetic investigations after ultrasonography findings including decreased fetal movements, hypoplastic male external genitalia, retrognathia, prefrontal edema, anomalies of the great vessels with pulmonary atresia and dilated tortuous aorta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Prenatal trio exome sequencing identified two homozygous likely pathogenic variants, i.e. a missense in <jats:italic>EFEMP2<\/jats:italic> involved in cutis laxa and a nonsense in <jats:italic>RAG1<\/jats:italic> involved in several types of severe combined immunodeficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The fetal ultrasonographic phenotype was partially compatible with previously reported prenatal presentations secondary to <jats:italic>EFEMP2<\/jats:italic> biallelic variants, but prenatal presentations have never been reported for <jats:italic>RAG1<\/jats:italic> related disorders because the <jats:italic>RAG1<\/jats:italic> phenotype is undetectable during pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both <jats:italic>EFEMP2<\/jats:italic> and <jats:italic>RAG1<\/jats:italic> variants were disclosed to the couple because the <jats:italic>EFEMP2<\/jats:italic> variant was considered causative for the fetal ultrasonographic phenotype and the <jats:italic>RAG1<\/jats:italic> variant was considered a finding of strong interest for genetic counselling and monitoring of future pregnancies following the American College of Medical Genetics and Genomics recommendations about the discovery of incidental findings in fetal exome sequencing in prenatal diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6629","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T03:48:46Z","timestamp":1719373726000},"page":"1115-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of pathogenic variants in <i>EFEMP2<\/i> and <i>RAG1<\/i> and undetectable fetal phenotype: A challenge of prenatal exome sequencing"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1011-875X","authenticated-orcid":false,"given":"Maud","family":"Favier","sequence":"first","affiliation":[{"name":"Inserm UMR1231 \u2010 GAD Universit\u00e9 Bourgogne Franche\u2010Comt\u00e9  Dijon France"},{"name":"SoFFoet \u2010 Soci\u00e9t\u00e9 Fran\u00e7aise de Foetopathologie  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Anomalies du d\u00e9veloppement et Syndromes Malformatifs FHU\u2010TRANSLAD  Dijon 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Maladies Rares Anomalies du d\u00e9veloppement et Syndromes Malformatifs FHU\u2010TRANSLAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3795-9456","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric Tran","family":"Mau\u2010Them","sequence":"additional","affiliation":[{"name":"Inserm UMR1231 \u2010 GAD Universit\u00e9 Bourgogne Franche\u2010Comt\u00e9  Dijon France"},{"name":"SoFFoet \u2010 Soci\u00e9t\u00e9 Fran\u00e7aise de Foetopathologie  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Anomalies du d\u00e9veloppement et Syndromes Malformatifs FHU\u2010TRANSLAD  Dijon 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