{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:25:57Z","timestamp":1769682357949,"version":"3.49.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary Multiple Osteochondromas (HMO) is a rare, pediatric skeletal disorder characterized by osteochondromas that form along the growth plates. These benign tumors can cause skeletal deformities, joint dysfunction, chronic pain and other health problems. Most HMO patients are born with a heterozygous mutation in\n                    <jats:italic>EXT1<\/jats:italic>\n                    or\n                    <jats:italic>EXT2<\/jats:italic>\n                    that encode Golgi enzymes responsible for heparan sulfate synthesis. However, prior studies have established that these mutations alone are insufficient to trigger osteochondroma formation, but additional genetic changes are needed. Loss\u2010of\u2010heterozygosity (LOH) has been invoked in some cases, but the full genomic landscape of osteochondromas remains unclear. Here, we carried out a proof\u2010of\u2010principle study and asked whether gene variants occur in osteochondromas in addition to\n                    <jats:italic>EXT<\/jats:italic>\n                    mutations, whether the variants are shared by osteochondromas in same or different patients and what putative pathogenic roles they may have. A total of 8 tumors from 4 patients were subjected to whole exome sequencing (WES) along with saliva DNA from the 4 patients and 3 parents that was used as specific reference. WES identified over 1,600 somatic single nucleotide variants or insertion\/deletions that were only partially shared amongst the tumors and were absent in the saliva DNA. Six genes were commonly mutated, including\n                    <jats:italic>PABC1<\/jats:italic>\n                    ,\n                    <jats:italic>TDG<\/jats:italic>\n                    and\n                    <jats:italic>ANKRD36<\/jats:italic>\n                    . These genes exert action which could directly or indirectly influence chondrogenesis, the first differentiation step in osteochondroma formation. The study reveals that osteochondromas do possess gene variants distinguishing them in the same or different patients. These traits could modulate their tumorigenic character and add complexity to HMO pathogenesis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical Significance:<\/jats:bold>\n                    This study provides insights into the genomic landscape of osteochondromas, potentially leading to development of disease diagnostic and prognostic tools.\n                  <\/jats:p>","DOI":"10.1002\/jor.70113","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:55:31Z","timestamp":1765641331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene Variants Characterize and Distinguish Osteochondromas in Patients With Hereditary Multiple Osteochondromas"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-5965","authenticated-orcid":false,"given":"Christina","family":"Mundy","sequence":"first","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadhana","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Talwar","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-4942","authenticated-orcid":false,"given":"Maurizio","family":"Pacifici","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Arkader","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Surgery The Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiographics.20.5.g00se171407"},{"key":"e_1_2_9_3_1","volume-title":"World Health Organization Classification of Tumours Lyon","author":"Fletcher C. 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