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.
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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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H. Sakaguchi and S. Yamashita contributed equally to this work.
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Sakaguchi, H., Yamashita, S., Miura, A. et al. A novel GJB1 frameshift mutation produces a transient CNS symptom of X-linked Charcot–Marie–Tooth disease. J Neurol 258, 284–290 (2011). https://doi.org/10.1007/s00415-010-5752-8
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DOI: https://doi.org/10.1007/s00415-010-5752-8