title: Clinicopathological features of centronuclear myopathy in Japanese populations harboring mutations in dynamin 2.
abstract: BACKGROUND
  Missense mutations in dynamin 2 gene (DNM2) are associated with autosomal dominant centronuclear myopathy (CNM) with characteristic histopathological findings of centrally located myonuclei in a large number of muscle fibers.
  
  
  METHODS
  To identify Japanese CNM caused by DNM2 mutations (DNM2-CNM), we sequenced DNM2 in 22 unrelated Japanese patients who were pathologically diagnosed with CNM. The clinical and pathological findings of DNM2-CNM in patients were reviewed.
  
  
  RESULTS
  We identified 3 different heterozygous missense mutations (p.E368K, p.R369W, and p.R465W) in 4 probands from 4 families. Clinically, calf muscle atrophy and pes cavus are features that are highly suggestive of DNM2-CNM among all CNMs. Pathologically, all 4 DNM2-CNM patients showed a radial distribution of myofibrils in scattered fibers, type 1 fiber atrophy, type 1 fiber predominance, and type 2C fibers. None of the non-DNM2-CNM patients exhibited all the 4 abovementioned pathological features, although some patients showed radial distribution without type 1 fiber atrophy and/or type 2C fibers.
  
  
  CONCLUSIONS
  These results indicate that the clinicopathological features of DNM2-CNM are rather homogeneous and can be distinguished from the features of non-DNM2-CNM.
authors.affiliation: Department of Neurology, National Center Hospital of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Mori-Yoshimura
authors.forename: Aya
authors.initials: A
authors.lastname: Okuma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Oya
authors.forename: Chieko
authors.initials: C
authors.lastname: Fujimura-Kiyono
authors.forename: Hideto
authors.initials: H
authors.lastname: Nakajima
authors.forename: Keita
authors.initials: K
authors.lastname: Matsuura
authors.forename: Aya
authors.initials: A
authors.lastname: Takemura
authors.forename: May Christine V
authors.initials: MC
authors.lastname: Malicdan
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy; D001344:Autopsy; D034285:Dynamin II / Q000235:genetics*; D004576:Electromyography; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000502:physiology*; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology*; D009431:Neural Conduction; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D034285:Dynamin II