MTM1 mutations in X-linked myotubular myopathy

Hum Mutat. 2000;15(5):393-409. doi: 10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R.


X-linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual-specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti-phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease-associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).

Publication types

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

MeSH terms

  • Alternative Splicing
  • DNA Transposable Elements
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multigene Family
  • Mutation*
  • Mutation, Missense
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / mortality
  • Polymorphism, Genetic
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Sequence Deletion
  • Survival Analysis
  • X Chromosome*


  • DNA Transposable Elements
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin