The identification of MAFB mutations in eight patients with multicentric carpo–tarsal osteolysis supports genetic homogeneity but clinical variability

Authors

  • Cybel Mehawej,

    1. Département de génétique, INSERM U781, Université Paris Descartes—Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France
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  • Jean-Benoît Courcet,

    1. Service de Pédiatrie1 et de Génétique Médicale, Hôpital d'Enfants, Centre Hospitalo-Universitaire, Dijon, France
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  • Geneviève Baujat,

    1. Département de génétique, INSERM U781, Université Paris Descartes—Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France
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  • Richard Mouy,

    1. Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique, Institut Imagine, Hôpital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Marion Gérard,

    1. Service de Génétique Médicale, Hôpital Clémenceau, Centre Hospitalo-Universitaire, Caen, France
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  • Isabelle Landru,

    1. Service de Néphrologie, Centre Hospitalier, Lisieux, France
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  • Morgane Gosselin,

    1. Service de Néphrologie, Centre Hospitalo-Universitaire Pontchaillou, Rennes, France
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  • Philippe Koehrer,

    1. Service d'Ophtalmologie, Hôpital Général, Dijon, France
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  • Christiane Mousson,

    1. Service de Néphrologie, Hôpital le Bocage, Centre Hospitalo-Universitaire, Dijon, France
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  • Sylvain Breton,

    1. Service de Radiologie Pédiatrique, Hôpital Necker Enfants Malades, Paris, France
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  • Pierre Quartier,

    1. Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique, Institut Imagine, Hôpital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris, Paris, France
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  • Martine Le Merrer,

    1. Département de génétique, INSERM U781, Université Paris Descartes—Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France
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  • Laurence Faivre,

    1. Service de Pédiatrie1 et de Génétique Médicale, Hôpital d'Enfants, Centre Hospitalo-Universitaire, Dijon, France
    2. Centre de Génétique et Centre de Référence Anomalies de Développement et Syndromes Malformatifs de l'interrégion Grand-Est, Hôpital d'Enfants, CHU, Dijon, France
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  • Valérie Cormier-Daire

    Corresponding author
    1. Département de génétique, INSERM U781, Université Paris Descartes—Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France
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  • Conflict of interest: none.
  • Cybel Mehawej and Jean-Benoît Courcet participated equally to the work.

Abstract

Multicentric carpo–tarsal osteolysis (MCTO) with or without nephropathy is a rare osteolysis disorder beginning in early childhood and involving mainly carpal and tarsal bones. Renal disease appears later in life in the majority of cases and evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance has been demonstrated, with a high frequency of sporadic cases. Recently, mutations in a highly conserved region of the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B) have been identified in MCTO patients by exome sequencing. MafB, known as a regulator of various developmental processes, is essential for osteoclastogenesis and renal development. We report here the molecular screening of MAFB in eight MCTO patients from six families. We identified MAFB mutations in all, including three novel missense mutations clustering within the hot spot mutation region. Among the eight patients, six only presented renal disease. Our report confirms the genetic homogeneity of MCTO and provides data underlying the clinical variability of this disorder. © 2013 Wiley Periodicals, Inc.

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