title: A novel GJB1 frameshift mutation produces a transient CNS symptom of X-linked Charcot-Marie-Tooth disease.
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.
authors.affiliation: Department of Neurology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Akiko
authors.initials: A
authors.lastname: Miura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirahara
authors.forename: En
authors.initials: E
authors.lastname: Kimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terasaki
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Hirano
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchino
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D017630:Connexins / Q000235:genetics*; D003680:Deglutition Disorders / Q000209:etiology; D004594:Electrophysiology; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D006987:Hypesthesia / Q000209:etiology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D009431:Neural Conduction; D010291:Paresis / Q000209:etiology; D010375:Pedigree; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000188:drug therapy / Q000235:genetics; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D016756:Immunoglobulins, Intravenous; D000097002:Gap Junction beta-1 Protein