CMT X: A novel GJB1 frameshift mutation produces a transient CNS symptom of

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J Neurol. 2010 Sep 21

A novel GJB1 frameshift mutation produces a transient CNS symptom of X-linked

Charcot-Marie-Tooth disease.

Sakaguchi H, Yamashita S, Miura A, Hirahara T, Kimura E, Maeda Y, Terasaki T,

Hirano T, Uchino M.

Department of Neurology, Faculty of Life Sciences, Kumamoto University, 1-1-1

Honjo, Kumamoto, 860-8556, Japan.

Abstract

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.