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

J Neurol. 2011 Feb;258(2):284-90. doi: 10.1007/s00415-010-5752-8. Epub 2010 Sep 21.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Charcot-Marie-Tooth Disease / complications
  • Charcot-Marie-Tooth Disease / drug therapy
  • Charcot-Marie-Tooth Disease / genetics
  • Connexins / genetics*
  • Deglutition Disorders / etiology
  • Electrophysiology
  • Female
  • Frameshift Mutation*
  • Humans
  • Hypesthesia / etiology
  • Immunoglobulins, Intravenous / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Molecular Sequence Data
  • Mothers
  • Mutation*
  • Neural Conduction
  • Paresis / etiology
  • Pedigree
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / drug therapy
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / genetics


  • Connexins
  • Immunoglobulins, Intravenous
  • connexin 32

Supplementary concepts

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