{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:55:28Z","timestamp":1773028528239,"version":"3.50.1"},"reference-count":6,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T00:00:00Z","timestamp":1707609600000},"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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A consanguineous couple was referred at 10\u00a0weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in <jats:italic>ASCC1<\/jats:italic> previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in <jats:italic>ASCC1<\/jats:italic> can usually include hydramnios, fetal hypo\u2010\/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in <jats:italic>CSPP1<\/jats:italic> associated with Joubert syndrome. Presentations in <jats:italic>CSPP1<\/jats:italic> include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10\u00a0+\u00a02 WG. Sanger prenatal diagnosis targeted on <jats:italic>ASCC1<\/jats:italic> and <jats:italic>CSPP1<\/jats:italic> variants showed the presence of the homozygous familial <jats:italic>ASCC1<\/jats:italic> variant. In this case, prenatal exome sequencing analysis is subject to a partial <jats:italic>ASCC1<\/jats:italic> phenotype and an undetectable <jats:italic>CSPP1<\/jats:italic> phenotype at 10\u00a0weeks of gestation. As <jats:italic>CSPP1<\/jats:italic> contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype\u2010genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting.<\/jats:p>","DOI":"10.1002\/pd.6519","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:09:05Z","timestamp":1707710945000},"page":"352-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early prenatal diagnosis of causative homozygous variants in <i>ASCC1<\/i> in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not?"],"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 \u2013 GAD Universit\u00e9 Bourgogne Franche\u2010Comt\u00e9  Dijon France"},{"name":"SoFFoet \u2013 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 CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Delanne","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Anomalies du d\u00e9veloppement et Syndromes malformatifs FHU\u2010TRANSLAD CHU Dijon Bourgogne  Dijon France"},{"name":"Centre Pluridisciplinaire de Diagnostic Pr\u00e9natal CHU Dijon Bourgogne  Dijon 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