title: Screening of the COL2A1 mutation in idiopathic osteonecrosis of the femoral head.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Faculty of Medicine, Department of Orthopaedic Surgery, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Takuaki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Orthopaedic Surgery, Kyushu Rosai Hospital, 1-1 Sonekitamachi, Kokuraminami-ku, Kitakyusyu, 800-0229, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000483:Alleles; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005091:Exons; D005260:Female; D005270:Femur Head / Q000473:pathology*; D005271:Femur Head Necrosis / Q000235:genetics* / Q000473:pathology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013256:Steroids / Q000737:chemistry
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D013256:Steroids
keywords: COL2A1; dysplasia; mutation; osteonecrosis