{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:08:56Z","timestamp":1762542536862},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,5,29]],"date-time":"2016-05-29T00:00:00Z","timestamp":1464480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Practical Research Project for Rare\/Intractable Diseases"},{"name":"RIKEN Junior Research Associate Program"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Idiopathic osteonecrosis of the femoral head (idiopathic ONFH) is an ischemic disorder resulting in necrosis of the subchondral bone of the femoral head. <jats:italic>COL2A1<\/jats:italic> mutations, including c.3508G&gt;A, have been reported to be involved in its etiology. However, the etiological role of <jats:italic>COL2A1<\/jats:italic> mutations in idiopathic ONFH remains controversial, because the pathology of idiopathic ONFH is ischemic necrosis, not epiphyseal dysplasia usually seen in the diseases caused by <jats:italic>COL2A1<\/jats:italic> mutations. The purpose of this study is to examine whether <jats:italic>COL2A1<\/jats:italic> mutations have causal relation with idiopathic ONFH or not. We recruited 1,451 Japanese patients with idiopathic ONFH, including steroid\u2010, alcohol\u2010, and neither steroid nor alcohol\u2010associated (neither\u2010associated) ONFH. The diagnosis was based on the criteria of the Japanese Research Committee on idiopathic ONFH of the Ministry of Health, Labour and Welfare. By whole\u2010exome sequencing, entire <jats:italic>COL2A1<\/jats:italic> coding regions and flanking introns were analyzed in 49 neither\u2010associated ONFH patients. In addition, the c.3508G&gt;A mutation of <jats:italic>COL2A1<\/jats:italic> was checked in all idiopathic ONFH patients using the invader assay. Whole\u2010exome sequencing did not detect any <jats:italic>COL2A1<\/jats:italic> mutations in the 49 patients. The c.3508G&gt;A mutation was not found in any of the 1,451 patients. In conclusion, <jats:italic>COL2A1<\/jats:italic> is unlikely to cause idiopathic ONFH. Epiphyseal dysplasia of the femoral head caused by <jats:italic>COL2A1<\/jats:italic> mutations may radiographically mimic idiopathic ONFH. <jats:italic>COL2A1<\/jats:italic> mutations should prompt clinical re\u2010evaluation of the patient's phenotype. \u00a9 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuaki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Orthopaedic Surgery Fukuoka University 7\u201045\u20101 Nanakuma, Jonan\u2010ku Fukuoka 814\u20100180 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama 236\u20100004 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama 236\u20100004 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aritoshi","family":"Iida","sequence":"additional","affiliation":[{"name":"Laboratory for Bone and Joint Diseases RIKEN Center for Integrative Medical Sciences 4\u20106\u20101 Shirokanedai, Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuharu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kyushu University 3\u20101\u20101 Maidashi, Higashi\u2010ku Fukuoka 812\u20108582 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Research Committee on Idiopathic Osteonecrosis of the Femoral Head of the Ministry of Health, Labour and Welfare of Japan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihide","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Kyushu Rosai Hospital 1\u20131 Sonekitamachi, Kokuraminami\u2010ku Kitakyusyu 800\u20100229 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