{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:54:50Z","timestamp":1790898890872,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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 diagnostic yield of integrated molecular autopsy (IMA) by combining deep post\u2010mortem phenotyping with exome (ES) and targeted genome sequencing (GS) for prenatally detected anomalies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      This retrospective study evaluated 28 perinatal cases (22 fetuses, six neonates) with severe anomalies, normal first\u2010tier genetics, and high consanguinity (42.9%). Deep phenotyping (radiography, macroscopy, histopathology) guided singleton ES (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a028), supplemented by GS (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014) for exome\u2010negative rescue or technical validation, and trio Sanger confirmation. The inter\u2010method agreement between morphological hypotheses and molecular diagnoses was assessed using Cohen's Kappa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The IMA established a molecular diagnosis in 19 of 28 cases (67.9% yield), with system\u2010specific yields of 100% in skeletal dysplasias (5\/5), 62.5% in central nervous system defects (5\/8), and 60% in cardiovascular malformations (3\/5). Autosomal recessive inheritance accounted for 52.6% (10\/19) of solved cases. The inter\u2010method agreement was substantial (Cohen\u2019s Kappa\u00a0=\u00a00.81,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Phenotypic expansions occurred in six cases (21.4%), while nine cases (32.1%) remained unexplained.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The IMA framework achieved a high diagnostic yield of 67.9% within a highly selected, consanguineous cohort. Although clinical yield and concordance are influenced by selection biases, comprehensive post\u2010mortem phenotyping remains essential to resolve atypical presentations, guide variant prioritization, and optimize reproductive counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.70264","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:14:17Z","timestamp":1790896457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Molecular Autopsy in a Highly Consanguineous Perinatal Cohort With Severe Malformations and Strong Genetic Susceptibility"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-0011","authenticated-orcid":false,"given":"Sihem","family":"Darouich","sequence":"first","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Tunis Universit\u00e9 de Tunis El Manar  Tunis Tunisia"},{"name":"Unit\u00e9 de Pathologie F\u0153tale et Placentaire CHU Habib Bougatfa  Bizerte Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Darouich","sequence":"additional","affiliation":[{"name":"Institut Sup\u00e9rieur des Sciences Humaines de Tunis Universit\u00e9 de Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Khemiri","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anatomie et Cytologie Pathologiques H\u00f4pital Menzel Bourguiba  Menzel Bourguiba Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorsaf","family":"Gtari","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anatomie et Cytologie Pathologiques H\u00f4pital Menzel Bourguiba  Menzel Bourguiba Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoudha","family":"Smiti","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anatomie et Cytologie 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