{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:58:32Z","timestamp":1790395112613,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the incremental diagnostic yield of sequencing in a large, well\u2010phenotyped international cohort of fetuses with prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify associated genes and variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective multicenter cohort study of fetuses with a prenatal diagnosis of ACC undergoing sequencing after nondiagnostic chromosomal microarray. Clinical data were obtained from prenatal ultrasound and fetal MRI reports. Cases were classified as isolated ACC, ACC with additional central nervous system (CNS) abnormalities, or ACC with extracranial abnormalities. Variants were classified according to the ACMG or ACGS criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 321 fetuses with ACC, a pathogenic or likely pathogenic (P\/LP) variant was identified in 97 cases (30.2%). Diagnostic yield increased with phenotypic complexity: 17.3% in isolated ACC, 25.7% in ACC with additional CNS abnormalities, and 41.0% in ACC with extracranial abnormalities. MRI confirmation was available in 249 cases (77.6%) and did not alter overall diagnostic yield of genetic testing. No significant difference in yield was observed between complete ACC and other ACC types. P\/LP variants were identified in 51 genes, most frequently\n                      <jats:italic>TUBA1A<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sequencing provides substantial diagnostic yield in prenatally diagnosed ACC, particularly when additional CNS or extracranial anomalies are present. These findings support the use of exome or genome sequencing in the prenatal evaluation of ACC and emphasize the importance of detailed phenotyping to improve classification, interpretation and counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.70252","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:05:14Z","timestamp":1790391914000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Yield of Sequencing in Prenatal Agenesis of the Corpus Callosum in a Well\u2010Phenotyped International Cohort"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-036X","authenticated-orcid":false,"given":"Lorraine","family":"Dugoff","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Perelman School of Medicine Divisions of Reproductive Genetics and Maternal Fetal Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-0740","authenticated-orcid":false,"given":"Natalie","family":"Chandler","sequence":"additional","affiliation":[{"name":"North Thames Genomic Laboratory Hub Great Ormond Street Hospital NHS Foundation Trust  London UK"},{"name":"Genetics and Genomics UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1511-613X","authenticated-orcid":false,"given":"Stephanie","family":"Allen","sequence":"additional","affiliation":[{"name":"West Midlands Genomics Laboratory Birmingham Women's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-2416","authenticated-orcid":false,"given":"Sarah A.","family":"Graham","sequence":"additional","affiliation":[{"name":"West Midlands Genomics Laboratory Birmingham Women's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Harrison","sequence":"additional","affiliation":[{"name":"Wessex Clinical Genetics Service Princess Anne Hospital  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"McCabe","sequence":"additional","affiliation":[{"name":"West Midlands Clinical Genetics Service Birmingham Women's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"de Burca","sequence":"additional","affiliation":[{"name":"Wessex Clinical Genetics Service Princess Anne Hospital  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Smith","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erina","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairead","family":"Hagarty","sequence":"additional","affiliation":[{"name":"Belfast Clinical Genetics Service Belfast Health and Social Care Trust  Belfast Northern Irelands UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5829-1961","authenticated-orcid":false,"given":"Juliana S.","family":"Gebb","sequence":"additional","affiliation":[{"name":"Richard D.\u00a0Wood Jr Center for Fetal Diagnosis and Treatment Department of General Thoracic and Fetal Surgery Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-0031","authenticated-orcid":false,"given":"Shelly","family":"Soni","sequence":"additional","affiliation":[{"name":"Richard D.\u00a0Wood Jr Center for Fetal Diagnosis and Treatment Department of General Thoracic and Fetal Surgery Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-6897","authenticated-orcid":false,"given":"Sonika","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Children's Hospital of Philadelphia Perelman School of Medicine at University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly G.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Children's Hospital of Philadelphia Perelman School of Medicine at University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2645-6767","authenticated-orcid":false,"given":"Haley M.","family":"Crane","sequence":"additional","affiliation":[{"name":"Richard D.\u00a0Wood Jr Center for Fetal Diagnosis and Treatment Department of General Thoracic and Fetal Surgery Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-1701","authenticated-orcid":false,"given":"Mary E.","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences and the Center for Maternal\u2010Fetal Precision Medicine University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6642","authenticated-orcid":false,"given":"Billie R.","family":"Lianoglou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences and the Center for Maternal\u2010Fetal Precision Medicine University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5387-7420","authenticated-orcid":false,"given":"Alex","family":"Gibbs","sequence":"additional","affiliation":[{"name":"North Thames Genomic Laboratory Hub Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-7138","authenticated-orcid":false,"given":"Lyn S.","family":"Chitty","sequence":"additional","affiliation":[{"name":"North Thames Genomic 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