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Homozygous deletion of an EGR2 enhancer in congenital amyelinating neuropathy

Authors

  • Benoît Funalot MD, PhD,

    Corresponding author
    1. National Referral Center for Rare Peripheral Neuropathies, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Department of Neurology, Centre Hospitalier Universitaire de Limoges, Limoges, France
    3. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
    4. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
    • Service de Neurologie, CHU de Limoges, 2 av Martin-Luther-King, 87042 Limoges Cedex, France
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  • Piotr Topilko PhD,

    1. Ecole Normale Superieure [no translation for this], Institute of Biology of the Ecole Normale Superieure, National Institute of Health and Medical Research Unit 1024, National Center for Scientific Research Unit 8197, Paris, France
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  • Maria Antonia Ramos Arroyo MD,

    1. Department of Medical Genetics, Navarre Health Services, [Virgen del Camino] Hospital, Pamplona, Spain
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  • Abdelaziz Sefiani MD, PhD,

    1. Human Genomics Center, School of Medicine and Pharmacy, [Mohamed V Souissi] University, Rabat, Morocco
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  • E. Tessa Hedley-Whyte MD,

    1. C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Department of Pathology, Harvard Medical School, Boston, MA
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  • Maria E. Yoldi MD,

    1. Department of Pediatrics, Navarre Health Services, [Virgen del Camino] Hospital, Pamplona, Spain
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  • Laurence Richard MSc,

    1. Department of Neurology, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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  • Estelle Touraille BSc,

    1. Department of Neurology, Centre Hospitalier Universitaire de Limoges, Limoges, France
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  • Mathieu Laurichesse BSc,

    1. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
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  • Emmanuel Khalifa MD,

    1. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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  • Jasmine Chauzeix MSc,

    1. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
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  • Adama Ouedraogo MSc,

    1. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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  • Didier Cros MD,

    1. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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  • Corinne Magdelaine PhD,

    1. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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  • Franck G. Sturtz MD, PhD,

    1. Department of Biochemistry and Molecular Genetics, University Hospital, Limoges, France, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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  • J. Andoni Urtizberea MD,

    1. Seaside Hospital of Paris, Hendaye, France
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  • Patrick Charnay PhD,

    1. Ecole Normale Superieure [no translation for this], Institute of Biology of the Ecole Normale Superieure, National Institute of Health and Medical Research Unit 1024, National Center for Scientific Research Unit 8197, Paris, France
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  • Federico Garcia Bragado MD,

    1. Department of Pathology, Navarre Health Services, [Virgen del Camino] Hospital, Pamplona, Spain
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  • Jean-Michel Vallat MD

    1. National Referral Center for Rare Peripheral Neuropathies, Centre Hospitalier Universitaire de Limoges, Limoges, France
    2. Department of Neurology, Centre Hospitalier Universitaire de Limoges, Limoges, France
    3. Research Team [Myelin Maintenance and Peripheral Neuropathies], University of Limoges Medical School, Limoges, France
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Abstract

The transcription factor EGR2 is expressed in Schwann cells, where it controls peripheral nerve myelination. Mutations of EGR2 have been found in patients with congenital hypomyelinating neuropathy or Charcot–Marie–Tooth disease type 1D. In a patient with congenital amyelinating neuropathy, we observed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice. This patient, born from consanguineous parents, showed no EGR2 immunoreactivity in Schwann cells and harbored a homozygous 10.7-kilobase-long deletion encompassing a myelin-specific enhancer of EGR2. This regulatory mutation is the first genetic abnormality associated with congenital amyelinating neuropathy in humans. ANN NEUROL 2012;

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