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A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family

Human Genetics volume 121, pages 625–629 (2007)Cite this article

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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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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Affiliations

  1. Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yoshinari Miyamoto & Shiro Ikegawa

  2. Department of Orthopedic Surgery, Tokyo Kosei Nenkin Hospital, Tokyo, Japan

    Tatsuo Matsuda

  3. Department of Orthopaedic Surgery, Nagoya University School of Medicine, Nagoya, Japan

    Hiroshi Kitoh

  4. Department of Rehabilitation Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Nobuhiko Haga

  5. Division of Medical Genetics and Division of Endocrinology and Metabolism, Saitama Children’s Medical Center, Iwatsuki, Japan

    Hirofumi Ohashi

  6. Department of Radiology, Tokyo Metropolitan Kiyose Children’s Hospital, Kiyose, Tokyo, Japan

    Gen Nishimura

Authors
  1. Yoshinari Miyamoto
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  2. Tatsuo Matsuda
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  3. Hiroshi Kitoh
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  4. Nobuhiko Haga
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  5. Hirofumi Ohashi
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  6. Gen Nishimura
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  7. Shiro Ikegawa
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Corresponding author

Correspondence to Shiro Ikegawa.

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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

Keywords

  • Slip Capital Femoral Epiphysis
  • COL2A1 Mutation
  • Multiple Epiphyseal Dysplasia
  • Subchondral Fracture
  • Bipartite Patella