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Connexin 32 promoter P2 mutations: A mechanism of peripheral nerve dysfunction

Authors

  • Henry Houlden MD,

    Corresponding author
    1. Department of Molecular Neurosciences, Institute of Neurology, Queen Square
    2. National Hospital for Neurology and Neurosurgery, Queen Square
    • The National Hospital for Neurology, Queen Square, London, WC1N 3BG, United Kingdom
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  • Mathilde Girard PhD,

    1. Genetique Moleculaire et Physiopathologie, INSERM U468, Hôpital Henri Mondor, Creteil, France
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  • Charles Cockerell MD,

    1. St. Bartholomew's Hospital and The Royal London Hospital, London
    2. Princess Alexandra Hospital, Harlow, Essex, United Kingdom
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  • David Ingram MD,

    1. St. Bartholomew's Hospital and The Royal London Hospital, London
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  • Nicholas W. Wood MD,

    1. Department of Molecular Neurosciences, Institute of Neurology, Queen Square
    2. National Hospital for Neurology and Neurosurgery, Queen Square
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  • Michel Goossens MD,

    1. Genetique Moleculaire et Physiopathologie, INSERM U468, Hôpital Henri Mondor, Creteil, France
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  • Rodney W. H. Walker MD,

    1. St. Bartholomew's Hospital and The Royal London Hospital, London
    2. Princess Alexandra Hospital, Harlow, Essex, United Kingdom
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  • Mary M. Reilly MD

    1. Department of Molecular Neurosciences, Institute of Neurology, Queen Square
    2. National Hospital for Neurology and Neurosurgery, Queen Square
    3. Center for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom
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Abstract

We identified a large Charcot–Marie–Tooth disease family with a novel mutation in the Connexin 32 (Cx32) P2 promoter region at position −526bp. This mutation was in a highly conserved SOX10 binding site. Functional studies were conducted on the Cx32 promoter that showed that this mutation reduced the activity of the Cx32 promoter and the affinity for SOX10 binding. These data suggest that interaction between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral nerve dysfunction. Ann Neurol, 2004

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