Journal of Neurology

, Volume 258, Issue 2, pp 284–290 | Cite as

A novel GJB1 frameshift mutation produces a transient CNS symptom of X-linked Charcot–Marie–Tooth disease

  • Hideya Sakaguchi
  • Satoshi YamashitaEmail author
  • Akiko Miura
  • Tomoo Hirahara
  • En Kimura
  • Yasushi Maeda
  • Tadashi Terasaki
  • Teruyuki Hirano
  • Makoto Uchino
Original Communication


X-linked Charcot–Marie–Tooth disease (CMT1X) is the second most common variant of CMT and is caused by mutations in the GJB1 gene encoding connexin 32. Some CMT1X patients with GJB1 missense mutations have shown transient central nervous system (CNS) symptoms with abnormal brain magnetic resonance imaging (MRI). Herein we report the first case with a novel GJB1 frameshift mutation that associates with a transient CNS symptom. The patient noticed high-arched feet and limited ankle dorsiflexion in early childhood; he transiently developed numbness and paresis of left face and arm, and dysphagia, with abnormal brain MRI. Although the CNS symptoms recovered within several hours without treatment, intravenous immunoglobulin (IVIg) therapy ameliorated progressing symptoms such as those of toe extensor muscles. His mother had been diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), and repetitive IVIg treatments had relieved the symptoms. Therefore, inflammation might be involved in the pathophysiology of CMT1X with the GJB1 mutation, while molecular analysis revealed that the mutant GJB1 was more rapidly degraded by the proteasome pathway known as endoplasmic reticulum (ER)-associated degradation.


X-linked Charcot–Marie–Tooth disease (CMT1X) GJB1 Connexin 32 Transient central nervous system symptoms Intravenous immunoglobulin (IVIg) treatment 



This work was partly supported by grants-in-aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labor, and Welfare of Japan.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hideya Sakaguchi
    • 1
  • Satoshi Yamashita
    • 1
    Email author
  • Akiko Miura
    • 1
  • Tomoo Hirahara
    • 1
  • En Kimura
    • 1
  • Yasushi Maeda
    • 1
  • Tadashi Terasaki
    • 2
  • Teruyuki Hirano
    • 1
  • Makoto Uchino
    • 1
  1. 1.Department of Neurology, Faculty of Life SciencesKumamoto UniversityKumamotoJapan
  2. 2.Department of NeurologyJapanese Red Cross Kumamoto HospitalKumamotoJapan

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