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CNS involvement in CMTX1 caused by a novel connexin 32 mutation: a 6-year follow-up in neuroimaging and nerve conduction

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Abstract

X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) is one of the most common inherited neurological disorders. Obvious CNS involvement is relatively rare in CMTX1 patients. A 24-year-old male with CMTX1 presented with three transient stroke-like attacks, and was followed up regularly for 6 years with brain MRI and electrophysiological examination. Transient symmetrical high signals on T2 imaging and restricted diffusion were found in bilateral deep white matter. Electrophysiological measurement revealed a sensorimotor peripheral neuropathy with slightly reduced nerve conduction velocities. A novel thymine to cytosine mutation at nucleotide position 445 in the connexin 32 allele of the GJB1 gene was identified. During the 6-year longitudinal study, patient’s motor and sensory function did not worsen; radiological abnormalities correlated with episodes of CNS dysfunction and resolved after clinical recovery; electrophysiological records showed no obvious change. Little change in the patient’s clinical, radiological and electrophysiological results over the follow-up reflected a slow disease progression.

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Abbreviations

CMAP:

Compound muscle action potential

CMT:

Charcot-Marie-Tooth disease

CMTX:

X-linked Charcot-Marie-Tooth disease

CMTX1:

X-linked Charcot-Marie-Tooth disease, type 1

CNS:

Central nervous system

Cx32:

Connexin 32

DWI:

Diffusion-weighted imaging

FLAIR:

Fluid attenuated inversion recovery

GJBI:

Gap junction beta 1

SNAP:

Sensory nerve action potential

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Acknowledgments

This work was supported by the National Natural Science Foundations of China (81230027, 81070959) and Key Scientific and Technological Project of Shanghai (11411950300). We thank the patients for their participation. We also thank Katherine Regan for editorial assistance.

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    Authors and Affiliations

    1. Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

      Chong Xie, Wei Liu, Xiaoqing Wang & Yangtai Guan

    2. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China

      Desheng Zhu

    3. Department of Neurology, Shanghai Yangpu Geriatric Hospital, Shanghai, China

      Hong Yang

    4. Department of Neurology, Renji Hospital, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, China

      Xiajun Zhou, Zezhi Li, Yong Hao & Yangtai Guan

    5. Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Suite 300, Philadelphia, PA, 19107, USA

      Guang-Xian Zhang

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    C. Xie and X. Zhou contributed equally to this work.

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    Xie, C., Zhou, X., Zhu, D. et al. CNS involvement in CMTX1 caused by a novel connexin 32 mutation: a 6-year follow-up in neuroimaging and nerve conduction. Neurol Sci 37, 1063–1070 (2016). https://doi.org/10.1007/s10072-016-2537-6

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