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A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families

Authors

  • Xu Wang,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Fuying Xiao,

    1. Department of Biotechnology, Guilin Medical College, Guangxi, P. R. China
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  • Qinbo Yang,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Bo Liang,

    1. Institute of Radiology, the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Zhaohui Tang,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Linbin Jiang,

    1. Department of Biotechnology, Guilin Medical College, Guangxi, P. R. China
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  • Qihui Zhu,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Wei Chang,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Jiuxi Jiang,

    1. Department of Biotechnology, Guilin Medical College, Guangxi, P. R. China
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  • Chuanming Jiang,

    1. Department of Biotechnology, Guilin Medical College, Guangxi, P. R. China
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  • Xiang Ren,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Jing-Yu Liu,

    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
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  • Qing K. Wang,

    Corresponding author
    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
    2. Department of Molecular Cardiology, Lerner Research Institute, and Center for Cardiovascular Genetics, The Cleveland Clinic Foundation, Cleveland, Ohio
    • Huazhong University of Science and Technology Human Genome Research Center, Wuhan 430074, P. R. China; Center for Cardiovascular Genetics, The Cleveland Clinic Foundation, Cleveland, OH 44195.
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  • Mugen Liu

    Corresponding author
    1. Human Genome Research Center and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
    • Huazhong University of Science and Technology Human Genome Research Center, Wuhan 430074, P. R. China.
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  • How to cite this article: Wang X, Xiao F, Yang Q, Liang B, Tang Z, Jiang L, Zhu Q, Chang W, Jiang J, Jiang C, Ren X, Liu J-Y, Wang QK, Liu M. 2006. A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. Am J Med Genet Part A 140A:1846–1853.

Abstract

Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five-generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2–4 fingers) with SYM1 families with mutations in the NOG gene or the family with mutation R438L recently reported in the GDF5 gene (encoding a bone morphogenetic protein family member). However, they show some unique features including the absence of cuboid bone, the lack of shortness of the first and fifth metacarpal bones, and manifestation of flat feet. Genome-wide linkage analysis of the two families mapped the disease gene to marker D20S112 with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K mutation in the GDF5 gene in both families. The mutation occurs at a highly conserved residue in the TGF-β domain of GDF5 and represents the second GDF5 mutation identified for SYM1 to date. The E491K mutation co-segregated with the affected individuals in the two families, and did not exist in unaffected family members or 200 normal controls. These results indicate that defects in GDF5 can cause SYM1 in the Chinese population, and expand the spectrum of clinical phenotypes associated with mutant GDF5. © 2006 Wiley-Liss, Inc.

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