Clinicopathological features of centronuclear myopathy in Japanese populations harboring mutations in dynamin 2

Clin Neurol Neurosurg. 2012 Jul;114(6):678-83. doi: 10.1016/j.clineuro.2011.10.040. Epub 2012 May 19.


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.

Discussion: These results indicate that the clinicopathological features of DNM2-CNM are rather homogeneous and can be distinguished from the features of non-DNM2-CNM.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Atrophy
  • Autopsy
  • Dynamin II / genetics*
  • Electromyography
  • Female
  • Gait Disorders, Neurologic / etiology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Muscle Weakness / etiology
  • Muscle, Skeletal / pathology
  • Mutation / physiology*
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology*
  • Neural Conduction
  • Pedigree
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Sequence Analysis, DNA
  • Young Adult


  • Dynamin II