Diagnosis of myotubular myopathy in the oldest known manifesting female carrier: a clinical and genetic study

Neuromuscul Disord. 2007 Feb;17(2):180-5. doi: 10.1016/j.nmd.2006.10.008. Epub 2007 Jan 23.


X-linked myotubular myopathy is a congenital myopathy due to mutation in the MTM1 gene, encoding myotubularin. Most of the affected male neonates die early of respiratory failure. The female carriers are usually asymptomatic. The authors report a novel MTM1 mutation in a 77-year-old woman. She presented with progressive ptosis since childhood, proximal limb weakness, and a severe restrictive respiratory dysfunction with a hemidiaphragmatic paresis, leading to death at 84 years of age. The muscle biopsy showed centrally nucleated fibers and mitochondrial abnormalities. A stop mutation Leu498X in MTM1 gene was identified in the proband and in her two healthy daughters. The X-inactivation pattern was random in the proband's blood and muscle DNA, and in blood DNA from her two unaffected MTM1 mutation carrier daughters. Two large heteroplasmic deletions were also detected in the muscle mitochondrial DNA of the propositus, raising the question of their putative impact on the phenotype.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Blepharoptosis / etiology
  • Blepharoptosis / genetics
  • Blotting, Southern
  • Chromosomes, Human, X
  • Creatine Kinase / blood
  • DNA / genetics
  • Dynamin II / genetics
  • Female
  • Heterozygote*
  • Humans
  • Lactic Acid / blood
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Myopathies, Structural, Congenital / diagnosis*
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Pedigree
  • Phenotype
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Respiratory Paralysis / genetics
  • Respiratory Paralysis / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tomography, X-Ray Computed


  • Lactic Acid
  • DNA
  • Creatine Kinase
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin
  • Dynamin II