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Screening of the COL2A1 mutation in idiopathic osteonecrosis of the femoral head
Author(s) -
Sakamoto Yuma,
Yamamoto Takuaki,
Miyake Noriko,
Matsumoto Naomichi,
Iida Aritoshi,
Nakashima Yasuharu,
Iwamoto Yukihide,
Ikegawa Shiro
Publication year - 2017
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23300
Subject(s) - femoral head , medicine , pathology , etiology , dysplasia , pathological , mutation , genetics , gene , biology , surgery
Idiopathic osteonecrosis of the femoral head (idiopathic ONFH) is an ischemic disorder resulting in necrosis of the subchondral bone of the femoral head. COL2A1 mutations, including c.3508G>A, have been reported to be involved in its etiology. However, the etiological role of COL2A1 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 COL2A1 mutations. The purpose of this study is to examine whether COL2A1 mutations have causal relation with idiopathic ONFH or not. We recruited 1,451 Japanese patients with idiopathic ONFH, including steroid‐, alcohol‐, and neither steroid nor alcohol‐associated (neither‐associated) 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‐exome sequencing, entire COL2A1 coding regions and flanking introns were analyzed in 49 neither‐associated ONFH patients. In addition, the c.3508G>A mutation of COL2A1 was checked in all idiopathic ONFH patients using the invader assay. Whole‐exome sequencing did not detect any COL2A1 mutations in the 49 patients. The c.3508G>A mutation was not found in any of the 1,451 patients. In conclusion, COL2A1 is unlikely to cause idiopathic ONFH. Epiphyseal dysplasia of the femoral head caused by COL2A1 mutations may radiographically mimic idiopathic ONFH. COL2A1 mutations should prompt clinical re‐evaluation of the patient's phenotype. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:768–774, 2017.