Genotype–phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD–DMD database: a model of nationwide knowledgebase

Authors

  • Sylvie Tuffery-Giraud,

    Corresponding author
    1. Université Montpellier 1, Faculté de Médecine, Montpellier, F-34000, France
    2. Inserm, U827, Montpellier, F-34000, France
    • Laboratoire de Génétique Moléculaire et Inserm U827, IURC, 641 Av du Doyen G. Giraud, 34093 Montpellier cedex 5, France
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    • The first two authors contributed equally to this work.

  • Christophe Béroud,

    1. Université Montpellier 1, Faculté de Médecine, Montpellier, F-34000, France
    2. Inserm, U827, Montpellier, F-34000, France
    3. CHU Montpellier, Laboratoire de génétique moléculaire, Montpellier, F-34000, France
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    • The first two authors contributed equally to this work.

  • France Leturcq,

    1. Hôpital Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Institut Cochin, Université Paris Descartes, INSERM Unité 567, Paris, France
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  • Rabah Ben Yaou,

    1. Hôpital Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Institut Cochin, Université Paris Descartes, INSERM Unité 567, Paris, France
    2. Inserm, U974, Paris, France
    3. UPMC Univ Paris 06, UMRS 974, Institut de Myologie, Paris, France
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  • Dalil Hamroun,

    1. Inserm, U827, Montpellier, F-34000, France
    2. CHU Montpellier, Laboratoire de génétique moléculaire, Montpellier, F-34000, France
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  • Laurence Michel-Calemard,

    1. Service d'endocrinologie moléculaire et maladies rares, Groupement hospitalier Est, Centre de Biologie et Pathologie, Bron, F-69677, France
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  • Marie-Pierre Moizard,

    1. CHRU de Tours, Service de Génétique, F-37044, France
    2. INSERM, U930, Tours, F-37044, France
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  • Rafaëlle Bernard,

    1. Laboratoire de génétique moléculaire, Hôpital des enfants de la Timone, Marseille, F-13385, France
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  • Mireille Cossée,

    1. Laboratoire de diagnostic génétique, Nouvel Hôpital Civil, Strasbourg, F-67091, France
    Current affiliation:
    1. Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Paris, France
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  • Pierre Boisseau,

    1. Laboratoire de génétique moléculaire, Institut de Biologie, CHU Hotel Dieu, Nantes, F-44093, France
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  • Martine Blayau,

    1. Laboratoire de génétique moléculaire, CHU Hôpital Pontchaillou, Rennes, F-35033, France
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  • Isabelle Creveaux,

    1. CHU Clermont Ferrand, Laboratoire de biochimie médicale et biologie moléculaire, Faculté de Médecine, Clermont Ferrand, F-63001, France
    2. Univ Clermont 1, UFR Médecine, Laboratoire de biochimie médicale, Clermont, Ferrand, F-63001, France
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  • Anne Guiochon-Mantel,

    1. Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, CHU de Bicêtre, Le Kremlin Bicêtre, F-94275, France
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  • Bérengère de Martinville,

    1. Laboratoire de génétique médicale, CHRU de Lille, Hôpital Jeanne de Flandre, Lille, F-59037, France
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  • Christophe Philippe,

    1. Laboratoire de génétique médicale, CHU de Nancy Hôpital d'adultes, Vandoeuvre-Les-Nancy, F-54511, France
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  • Nicole Monnier,

    1. Laboratoire de biochimie et génétique moléculaire, CHU de Grenoble, Hôpital Albert, Grenoble, F-38043, France
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  • Eric Bieth,

    1. Laboratoire de génétique médicale, CHU Hôpital Purpan, Toulouse, F-31059, France
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  • Philippe Khau Van Kien,

    1. CHU Montpellier, Laboratoire de génétique moléculaire, Montpellier, F-34000, France
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  • François-Olivier Desmet,

    1. Inserm, U827, Montpellier, F-34000, France
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  • Véronique Humbertclaude,

    1. Inserm, U827, Montpellier, F-34000, France
    2. CHU Montpellier, Laboratoire de génétique moléculaire, Montpellier, F-34000, France
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  • Jean-Claude Kaplan,

    1. Hôpital Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Institut Cochin, Université Paris Descartes, INSERM Unité 567, Paris, France
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  • Jamel Chelly,

    1. Hôpital Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Institut Cochin, Université Paris Descartes, INSERM Unité 567, Paris, France
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  • Mireille Claustres

    1. Université Montpellier 1, Faculté de Médecine, Montpellier, F-34000, France
    2. Inserm, U827, Montpellier, F-34000, France
    3. CHU Montpellier, Laboratoire de génétique moléculaire, Montpellier, F-34000, France
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  • Communicated by Jurgen Horst

Abstract

UMD–DMD France is a knowledgebase developed through a multicenter academic effort to provide an up-to-date resource of curated information covering all identified mutations in patients with a dystrophinopathy. The current release includes 2,411 entries consisting in 2,084 independent mutational events identified in 2,046 male patients and 38 expressing females, which corresponds to an estimated number of 39 people per million with a genetic diagnosis of dystrophinopathy in France. Mutations consist in 1,404 large deletions, 215 large duplications, and 465 small rearrangements, of which 39.8% are nonsense mutations. The reading frame rule holds true for 96% of the DMD patients and 93% of the BMD patients. Quality control relies on the curation by four experts for the DMD gene and related diseases. Data on dystrophin and RNA analysis, phenotypic groups, and transmission are also available. About 24% of the mutations are de novo events. This national centralized resource will contribute to a greater understanding of prevalence of dystrophinopathies in France, and in particular, of the true frequency of BMD, which was found to be almost half (43%) that of DMD. UMD–DMD is a searchable anonymous database that includes numerous newly developed tools, which can benefit to all the scientific community interested in dystrophinopathies. Dedicated functions for genotype-based therapies allowed the prediction of a new multiexon skipping (del 45–53) potentially applicable to 53% of the deleted DMD patients. Finally, such a national database will prove to be useful to implement the international global DMD patients' registries under development. Hum Mutat 30:1–12, 2009. © 2009 Wiley-Liss, Inc.

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