{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:20:09Z","timestamp":1778674809932,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore potential genetic contributors across different subtypes of isolated neural tube defects (NTDs) \u2010 acrania\u2013exencephaly\u2013anencephaly sequence (AEAS), spinal dysraphism, and encephalocele \u2010 using exome sequencing (ES) in a prenatal cohort, with the goal of gaining insight into the molecular diversity underlying these distinct phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed all fetuses diagnosed prenatally with isolated NTDs at Tel Aviv Sourasky Medical Center between September 2020 and July 2025. Detailed anatomical ultrasound excluded additional malformations. Chromosomal microarray (CMA) and trio\u2010based ES were performed using standard protocols. Variant interpretation followed ACMG\/AMP guidelines, integrating phenotypic concordance via Human Phenotype Ontology (HPO) terms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort comprised 23 fetuses: 10 with AEAS (9 acrania, 1 exencephaly), 8 with spinal dysraphism (5 myelomeningocele, 3 meningocele), and 5 with encephalocele. Across the cohort, exome sequencing yielded pathogenic or likely pathogenic variants in 26% (6\/23) of cases and a variant of uncertain significance in 4% (1\/23). Detection rates varied by subtype, highest in encephalocele (60%), followed by spinal dysraphism (25%) and AEAS (20%). However, these findings reflect diagnostic associations rather than definitive causal relationships. Identified genes included\n                      <jats:italic>PPP1R12A<\/jats:italic>\n                      ,\n                      <jats:italic>ARHGAP35, PIEZO2, KIAA0586, TSC2<\/jats:italic>\n                      , and\n                      <jats:italic>CLCN7<\/jats:italic>\n                      , representing diverse pathways in cytoskeletal organization, ciliary function, mechanotransduction, and mTOR signaling. Notably, recurrent\n                      <jats:italic>PPP1R12A<\/jats:italic>\n                      variants were found in 2 fetuses: one with AEAS and one with encephalocele, suggesting a shared morphogenetic pathway affecting cranial fold formation and mesenchymal remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that these distinct types of NTD, namely AEAS, spinal dysraphism, and encephalocele, may represent partially divergent embryologic and genetic entities rather than a single phenotypic continuum. Subtype\u2010specific analysis revealed differing molecular patterns, emphasizing the value of trio\u2010based ES in elucidating the etiology of isolated NTDs. Larger studies are needed to refine detection rates and expand our understanding of the genetic architecture underlying these distinct malformations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.70102","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:45:02Z","timestamp":1771559102000},"page":"842-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exome Sequencing in Prenatally Diagnosed Isolated Neural Tube Defects: A Subtype\u2010Specific Analysis"],"prefix":"10.1002","volume":"46","author":[{"given":"Adi","family":"Botvinik","sequence":"first","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vered Offen","family":"Glasner","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adi","family":"Reches","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9941-0215","authenticated-orcid":false,"given":"Hadas","family":"Miremberg","sequence":"additional","affiliation":[{"name":"Division of OB\/GYN Ultrasound Lis Women's and Maternity Hospital Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina Krajden","family":"Haratz","sequence":"additional","affiliation":[{"name":"Division of OB\/GYN Ultrasound Lis Women's and Maternity Hospital Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tal","family":"brill","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liron","family":"Malki","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Rozenzwaig","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-7668","authenticated-orcid":false,"given":"Yuval","family":"Yaron","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-3732","authenticated-orcid":false,"given":"Michal","family":"Levy","sequence":"additional","affiliation":[{"name":"Prenatal Genetic Diagnosis Unit Genetics Institute Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Faculty of Medicine Tel Aviv University  Tel Aviv 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