title: Myotonia in DNM2-related centronuclear myopathy.
abstract: Centronuclear myopathy (CNM) is a rare hereditary myopathy characterized by centrally located muscle fiber nuclei. Mutations in the dynamin 2 (DNM2) gene are estimated to account for about 50 % of CNM cases. Electromyographic recordings in CNM may show myopathic motor unit potentials without spontaneous activity at rest. Myotonic discharges, a distinctive electrical activity caused by membrane hyperexcitability, are characteristic of certain neuromuscular disorders. Such activity has been reported in only one CNM case without a known genetic cause. We sequenced the DNM2 gene and the genes associated with myotonia (CLCN1, SCN4A, DMPK and ZNF9) in a sporadic adult patient with CNM and myotonic discharges. Sequencing the entire coding region and exon-intron boundaries revealed a heterozygous c.1106g-a substitution in exon 8, resulting in a R369Q change in the DNM2. Sequencing the CLCN1, SCN4A, DMPK and ZNF9 genes ruled out mutations in these genes. This is the first report of DNM2-related CNM presenting with myotonia. The diagnosis of CNM should be considered in patients with myotonic discharges of an unknown cause.
authors.affiliation: Departments of Neurology, Edith Wolfson Medical Center, 58100, Holon, Israel, ronda@post.tau.ac.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Dabby
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.forename: Ronit
authors.initials: R
authors.lastname: Gilad
authors.forename: Karin
authors.initials: K
authors.lastname: Jurkat-Rott
authors.forename: Frank
authors.initials: F
authors.lastname: Lehmann-Horn
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
mesh_terms: D000328:Adult; D001483:Base Sequence; D018118:Chloride Channels / Q000235:genetics; D004252:DNA Mutational Analysis; D034285:Dynamin II / Q000235:genetics*; D004576:Electromyography; D005260:Female; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D020914:Myopathies, Structural, Congenital / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009222:Myotonia / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D065636:Myotonin-Protein Kinase / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: C086321:CLC-1 channel; C433227:CNBP protein, human; D018118:Chloride Channels; C585517:DMPK protein, human; D062553:NAV1.4 Voltage-Gated Sodium Channel; D016601:RNA-Binding Proteins; C106251:SCN4A protein, human; D065636:Myotonin-Protein Kinase; D034285:Dynamin II