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Mutations in the prostaglandin transporter encoding gene SLCO2A1 Cause primary hypertrophic osteoarthropathy and isolated digital clubbing

Authors

  • Wenke Seifert,

    1. Institute for Vegetative Anatomy, Charité—University Medicine of Berlin, Berlin, Germany
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    • These two authors contributed equally to this work.

  • Jirko Kühnisch,

    1. Institute of Genetics and Human Genetics, Charité—University Medicine of Berlin, Berlin, Germany
    2. Development and Disease Group, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
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    • These two authors contributed equally to this work.

  • Beyhan Tüysüz,

    1. Cerrahpasa Medical Faculty, Department of Pediatric Genetics, Istanbul University, Istanbul, Turkey
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  • Christof Specker,

    1. Department of Rheumatology and Clinical Immunology, Centre for Internal Medicine, Kliniken Essen Süd, Essen, Germany
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  • Ad Brouwers,

    1. Department of Internal Medicine, Gelderse Vallei Hospital, Ede, The Netherlands
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  • Denise Horn

    Corresponding author
    1. Institute of Genetics and Human Genetics, Charité—University Medicine of Berlin, Berlin, Germany
    • Institute of Genetics and Human Genetics, Charité-–University Medicine of Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
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  • Communicated by Ravi Savarirayan

Abstract

Digital clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder with variable digital clubbing as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found to cause PHO. Here, we identified three unrelated families with different mutations in the prostaglandin transporter (PGT) encoding gene SLCO2A1 which presumably result in reduced metabolic clearance by 15-PGDH due to diminished cellular uptake of prostaglandin E2 (PGE2) by mutant PGT. In two consanguineous families, homozygous mutations, an intragenic deletion that results in frameshift and a missense mutation, are associated with a severe PHO phenotype. In a third family, a heterozygous carrier of a stop mutation presents with isolated digital clubbing. Thus, our study further supports the importance of PGE2 metabolism in the pathogenesis of digital clubbing and PHO. Hum Mutat 33:660–664, 2012. © 2012 Wiley Periodicals, Inc.

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