Abstract
Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity. Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases.
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References
Caffey J (1968) The early roentgenographic changes in essential coxa plana: their significance in pathogenesis. Am J Roentgenol Radium Ther Nucl Med 103:620–634
Catterall A (1971) The natural history of Perthes’ disease. J Bone Joint Surg Br 53:37–53
Chen WM, Liu YF, Lin MW, Chen IC, Lin PY, Lin GL, Jou YS, Lin YT, Fann CS, Wu JY, Hsiao KJ, Tsai SF (2004) Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13. Am J Hum Genet 75:310–317
Dilley A, Hooper WC, Austin H, Jamil M, Miller C, Stokes M, Evatt B, Eldridge J (2003) The beta fibrinogen gene G-455-A polymorphism is a risk factor for Legg-Perthes disease. J Thromb Haemost 1:2317–2321
Glueck CJ, Crawford A, Roy D, Freiberg R, Glueck H, Stroop D (1996) Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease. J Bone Joint Surg Am 78:3–13
Glueck CJ, Freiberg RA, Crawford A, Gruppo R, Roy D, Tracy T, Sieve-Smith L, Wang P (1998) Secondhand smoke, hypofibrinolysis, and Legg-Perthes disease. Clin Orthop Relat Res 352:159–167
Gruppo R, Glueck CJ, Wall E, Roy D, Wang P (1998) Legg-Perthes disease in three siblings, two heterozygous and one homozygous for the factor V Leiden mutation. J Pediatr 132:885–888
Hall DJ (1986) Genetic aspects of Perthes’ disease. A critical review. Clin Orthop Relat Res 209:100–114
Liu YF, Chen WM, Lin YF, Yang RC, Lin MW, Li LH, Chang YH, Jou YS, Lin PY, Su JS, Huang SF, Hsiao KJ, Fann CS, Hwang HW, Chen YT, Tsai SF (2005) Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med 352:2294–2301
Mackenzie WG, Bassett GS, Mandell GA, Scott CI Jr (1989) Avascular necrosis of the hip in multiple epiphyseal dysplasia. J Pediatr Orthop 9:666–671
Margetts BM, Perry CA, Taylor JF, Dangerfield PH (2001) The incidence and distribution of Legg-Calve-Perthes’ disease in Liverpool, 1982–1995. Arch Dis Child 84:351–354
Mazda K, Pennecot GF, Zeller R, Taussig G (1999) Perthes’ disease after the age of twelve years. Role of the remaining growth. J Bone Joint Surg Br 81:696–698
Miyamoto Y, Nakashima E, Hiraoka H, Ohashi H, Ikegawa S (2005) A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia. Hum Genet 118:175–178
Nishimura G, Haga N, Kitoh H, Tanaka Y, Sonoda T, Kitamura M, Shirahama S, Itoh T, Nakashima E, Ohashi H, Ikegawa S (2005) The phenotypic spectrum of COL2A1 mutations. Hum Mutat 26:36–43
Noltorp S, Kristoffersson UL, Mandahl N, Stigsson L, Svensson B, Werner CO (1986) Trichorhinophalangeal syndrome type I: symptoms and signs, radiology and genetics. Ann Rheum Dis 45:31–36
Pillai A, Atiya S, Costigan PS (2005) The incidence of Perthes’ disease in Southwest Scotland. J Bone Joint Surg Br 87:1531–1535
Ponseti IV, Maynard JA, Weinstein SL, Ippolito EG, Pous JG (1983) Legg-Calve-Perthes disease. Histochemical and ultrastructural observations of the epiphyseal cartilage and physis. J Bone Joint Surg Am 65:797–807
Rowe SM, Jung ST, Lee KB, Bae BH, Cheon SY, Kang KD (2005) The incidence of Perthes’ disease in Korea: a focus on differences among races. J Bone Joint Surg Br 87:1666–1668
Thompson GH, Price CT, Roy D, Meehan PL, Richards BS (2002) Legg-Calve-Perthes disease: current concepts. Instr Course Lect 51:367–384
Wamoscher Z, Farhi A (1963) Hereditary Legg-Calve-Perthes disease. Am J Dis Child 106:97–100
Williams CJ, Considine EL, Knowlton RG, Reginato A, Neumann G, Harrison D, Buxton P, Jimenez S, Prockop DJ (1993) Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75–>Cys mutation in the procollagen type II gene (COL2A1). Hum Genet 92:499–505
Acknowledgements
We thank the patients and their family for their cooperation, Dr. Hidekazu Touga for supporting the research, Dr. Kazuharu Takikawa for valuable advice and critical reading of the manuscript and Yoshie Takanashi for the excellent technical assistance. This work was supported by Grants-in-aid from Research on Child Health and Development from Ministry of Health, Labor and Welfare of Japan (Contract grant number: 17C-1, H18-005) and from Ministry of Education, Culture, Sports and Science of Japan (Contract grant number: 18390423).
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Miyamoto, Y., Matsuda, T., Kitoh, H. et al. A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family. Hum Genet 121, 625–629 (2007). https://doi.org/10.1007/s00439-007-0354-y
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DOI: https://doi.org/10.1007/s00439-007-0354-y