Molecular genetics of triplet repeats: unstable expansion of triplet repeats as a new mechanism for neurodegenerative diseases

Intern Med. 1997 Jan;36(1):3-8. doi: 10.2169/internalmedicine.36.3.


Expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases including spinal and bulbar muscular atrophy (SBMA), Huntington's disease, dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), fragile X syndrome, myotonic dystrophy and Friedreich's ataxia. These diseases share unique features, which are difficult to explain based on Mendelian inheritance. These unique clinical genetic features include genetic anticipation and a broad spectrum of clinical presentations, which have been shown to be associated with the instability of the trinucleotide repeats. Recent studies suggest that gene products with expanded polyglutamine tracts may be toxic to neuronal cells, and the mechanisms of neurotoxicity should be thoroughly investigated. To develop therapeutic measures, creation of animal models or cell culture systems for the investigation of neurotoxicity will be indispensable.

Publication types

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

MeSH terms

  • Age of Onset
  • Animals
  • Humans
  • Minisatellite Repeats*
  • Molecular Biology
  • Nervous System Diseases / classification
  • Nervous System Diseases / etiology
  • Nervous System Diseases / genetics*
  • Phenotype
  • Trinucleotide Repeats*