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Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation

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Abstract

Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported in patients with Charcot–Marie–Tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed resequencing array that simultaneously screens for 28 CMT-associated genes. Electrophysiological studies revealed that the patient and her healthy mother had demyelinating polyneuropathy. Furthermore, they showed the same novel mutation in the early growth response 2 (EGR2) gene. Recognizing pre-existing asymptomatic CMT by electrophysiological studies and genetic analysis before VCR treatment allowed us to prevent severe VCR-induced neuropathy.

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Acknowledgements

We thank the families described in this report for their cooperation. We also thank Ms. A. Yoshimura of Kagoshima University for her excellent technical assistance.

Disclosures

This study was supported in part by grants from the Nervous and Mental Disorders and Research Committee for Charcot–Marie–Tooth Disease, Neuropathy, Ataxic Disease and Research on Applying Health Technology of the Japanese Ministry of Health, Welfare and Labor (H.T). H.T. has received royalty from Athena diagnostics.

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Authors and Affiliations

  1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima City, Kagoshima, 890-8520, Japan

    Tomonori Nakamura, Akihiro Hashiguchi, Shoko Tokunaga & Hiroshi Takashima

  2. Department of Hematology and Immunology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima City, Kagoshima, 890-8520, Japan

    Shinsuke Suzuki & Kimiharu Uozumi

Authors
  1. Tomonori Nakamura
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  2. Akihiro Hashiguchi
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  3. Shinsuke Suzuki
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  4. Kimiharu Uozumi
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  5. Shoko Tokunaga
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  6. Hiroshi Takashima
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Correspondence to Hiroshi Takashima.

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Nakamura, T., Hashiguchi, A., Suzuki, S. et al. Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation. Neurogenetics 13, 77–82 (2012). https://doi.org/10.1007/s10048-012-0313-1

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  • DOI: https://doi.org/10.1007/s10048-012-0313-1

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