Trinucleotide repeat disorders

Annu Rev Neurosci. 2007;30:575-621. doi: 10.1146/annurev.neuro.29.051605.113042.

Abstract

The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy. The dynamic nature of these mutations provided an explanation for the variable phenotype expressivity within a family. Beyond diagnosis and genetic counseling, the benefits from studying these disorders have been noted in both neurobiology and cell biology. Examples include insight about the role of translational control in synaptic plasticity, the role of RNA processing in the integrity of muscle and neuronal function, the importance of Fe-S-containing enzymes for cellular energy, and the dramatic effects of altering protein conformations on neuronal function and survival. It is exciting that within a span of 15 years, pathogenesis studies of this class of disorders are beginning to reveal pathways that are potential therapeutic targets.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Cerebellar Ataxia / genetics
  • Cerebellar Ataxia / metabolism
  • Cerebellar Ataxia / physiopathology
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism
  • Fragile X Syndrome / physiopathology
  • Genetic Predisposition to Disease / genetics*
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Heredodegenerative Disorders, Nervous System / metabolism
  • Heredodegenerative Disorders, Nervous System / physiopathology
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Huntington Disease / physiopathology
  • Mutation / genetics
  • Peptides / genetics
  • Peptides / metabolism
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • Peptides
  • polyglutamine