{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:13:44Z","timestamp":1791252824400,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Congenital limb anomalies remain without an etiological diagnosis in up to 65% of patients. To help close this gap, we describe the genetic diagnostic outcomes of a large cohort. Patients whose primary indication for genetic consultation was a limb anomaly were included from 2014 to 2024. Demographic, investigation, and diagnostic information were extracted, described, and compared. One hundred and thirty\u2010two patients were included in the final cohort, with an average molecular diagnostic yield of 36%. The most common conditions were polydactyly (24%) and radial anomalies (19%). Fifty percent had syndromic features. Seven (5%) patients underwent chromosomal microarray (CMA) only, 81 (63%) CMA and a gene panel, and 43 (32%) subsequently underwent exome sequencing. Exome yielded a diagnosis in 11 (25%). We identified 25 novel mutations in known disease\u2010causing genes, including\n                    <jats:italic>TBX3<\/jats:italic>\n                    (3 cases) and expanded the phenotype of several loci, including\n                    <jats:italic>BMP4<\/jats:italic>\n                    and\n                    <jats:italic>HNRNPH2<\/jats:italic>\n                    . Finally, we identified two new limb anomalies candidate loci, for which previously published mouse studies from other groups suggested roles in limb development:\n                    <jats:italic>HOXA11<\/jats:italic>\n                    and a 2q31.1 deletion involving\n                    <jats:italic>HOXD10<\/jats:italic>\n                    and\n                    <jats:italic>HOXD12<\/jats:italic>\n                    . This represents the second largest described limb anomalies cohort. Exome\u2010wide sequencing associated with literature and database searches for mouse data represents an opportunity to identify novel etiologies in this group of disorders, including two candidate loci we identified.\n                  <\/jats:p>","DOI":"10.1111\/cge.70048","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T06:41:12Z","timestamp":1755844872000},"page":"424-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Landscape in Limb Anomalies: Diagnostic Yield and New Candidate Genes"],"prefix":"10.1111","volume":"109","author":[{"given":"Akram","family":"Mokhtari","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Charbonneau","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-1968","authenticated-orcid":false,"given":"Valancy","family":"Miranda","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadij\u00e9","family":"Jizi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Ange","family":"Delrue","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Egerszegi","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Department of Surgery CHU Sainte\u2010Justine  Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7987-6731","authenticated-orcid":false,"given":"Isabelle","family":"Thiffault","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Mercy Kansas City  Kansas City Missouri USA"},{"name":"Department of Pathology and Laboratory Medicine Children's Mercy Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-7107","authenticated-orcid":false,"given":"Philippe M.","family":"Campeau","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics CHU Sainte\u2010Justine  Montreal Quebec 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