{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T07:10:22Z","timestamp":1764141022701,"version":"3.46.0"},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Multiple epiphyseal dysplasia (MED, OMIM #600969) is sometimes a mild skeletal dysplasia with diverse clinical findings, including early\u2010onset osteoarthritis and short stature. Radiographic surveys can identify delayed epiphyseal ossification and cartilaginous changes. Due to genetic heterogeneity in MED, with dominant or recessive inheritance, molecular testing is essential for its diagnosis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The clinical manifestations, the results of laboratory examinations, and genetic analysis of a 14\u2010year\u2010old Pakistani male with MED are reported.<\/jats:p>\n <\/jats:sec>\n \n Case Presentation<\/jats:title>\n \n Here we present a male patient with type\u20101 diabetes and hypothyroidism with bilateral knee effusions, right knee flexion contracture, and chronic arthralgias in his elbows and wrists. Given his symptomatology, a diagnosis of juvenile idiopathic arthritis (JIA) was initially suspected. Radiographs revealed sclerotic changes and fragments in the femoral and tibial epiphyses, suggesting destructive arthropathy. Genetic testing identified a\n COL9A3<\/jats:italic>\n variant (c.148\u20101G>C), as well as CTLA4 deficiency. The\n COL9A3<\/jats:italic>\n gene produces type IX collagen, and mutations in this gene can disrupt collagen folding or its interaction with other cartilage components. Complications include joint damage and early osteoarthritis, possibly requiring surgery.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n To date, only three\n COL9A3<\/jats:italic>\n splice\u2010site mutations have been linked to MED. Our patient's splicing variant (c.148\u20101G>C) is novel and is likely causative, based on similar pathogenic mutations. Our patient presented with symptoms suggestive of JIA, but radiographic findings were inconsistent with this diagnosis. Genetic testing revealed a new pathogenic splicing variant in the\n COL9A3<\/jats:italic>\n gene, confirming MED.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This case highlights the importance of early molecular testing if radiographic sclerotic changes are seen in the epiphyses due to the clinical and genetic heterogeneity of MED.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70147","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T08:39:35Z","timestamp":1762418375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exome Sequencing Identifies a Novel Splicing Variant in\n COL9A3<\/i>\n Resulting in Multiple Epiphyseal Dysplasia: A Case Report"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6804-7187","authenticated-orcid":false,"given":"Bashayer","family":"Alnuaimi","sequence":"first","affiliation":[{"name":"Division of Rheumatology Montreal Children's Hospital Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-1968","authenticated-orcid":false,"given":"Valancy","family":"Miranda","sequence":"additional","affiliation":[{"name":"Medical Genetics Service Sainte\u2010Justine Hospital Center Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Marie","family":"Sbrocchi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Montreal Children's Hospital Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe M.","family":"Campeau","sequence":"additional","affiliation":[{"name":"Medical Genetics Service Sainte\u2010Justine Hospital Center Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Campillo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Montreal Children's Hospital Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-4945","authenticated-orcid":false,"given":"Piya","family":"Lahiry","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Montreal Children's Hospital Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-D-13-00173"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1212"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10066"},{"volume-title":"GeneReviews","year":"2024","author":"Briggs M. D.","key":"e_1_2_11_5_1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/324023"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453670903473032"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705301200"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-199805000-00023"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-15-371"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000131)90:3<216::AID-AJMG6>3.0.CO;2-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30411"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/302328"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.055"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.36.8.621"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2007.11.009"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T07:06:06Z","timestamp":1764140766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/mgg3.70147"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70147","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70147"}}