Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy

Neuromuscul Disord. 2007 Jul;17(7):562-8. doi: 10.1016/j.nmd.2007.03.010. Epub 2007 May 29.


We aimed to correlate pathologic findings with MTM1 mutation type in a series of molecularly defined XLMTM cases. Clinical data from 15 XLMTM patients and their corresponding 16 muscle biopsies were studied. All patients were infants (range: 6-217 days old) when initially biopsied. The proportion of myofibers with central nuclei did not correlate with clinical outcome, however, morphometric studies showed that survivors had larger myofiber diameters in infancy than those who died (10.4+/-3.9microm versus 8.9+/-3microm; p<0.001). As a corollary, patients with MTM1 missense mutations had larger myofiber diameters (11.1+/-4microm), than those with truncation/deletion mutations (8.6+/-2.7microm) (controls 11.7+/-2.5microm) (p<0.0001). These data indicate that differences in myofiber size correlate with MTM1 mutation type and patient outcome. Failure to attain and/or maintain myofiber size, along with fiber type perturbations and the misplacement of myofiber nuclei and other organelles, are important components of XLMTM muscle pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microscopy, Electron, Transmission / methods
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Fibers, Skeletal / ultrastructure
  • Mutation*
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Statistics as Topic


  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin