Introduction to Trinucleotide Repeat Diseases

H. Brent Clark

Research output: Chapter in Book/Report/Conference proceedingChapter


Neurological diseases caused by trinucleotide repeat expansions typically involve the spinocerebellar, extrapyramidal or primary motor systems. The inheritance patterns of these disorders range from autosomal recessive, to autosomal dominant to X-linked. The common mechanism is an expanded tandem-repeat of a trinucleotide (rarely a tetra-or pentanucleotide) sequence. A number of these conditions, notably Huntington's disease, spinobulbar muscular atrophy and several of the dominantly inherited ataxias, are characterized by CAG-repeats coding for an expanded polyglutamine tract within the mutant protein. This expansion presumably causes the mutant protein to have a novel function different from the native protein. Other mechanisms include intronic expansions which impede splicing of message in Friedreich's ataxia, resulting in a relative loss of function of the frataxin protein. Diseases such as spinocerebellar ataxia 8, spinocerebellar ataxia 31 and the myotonic dystrophies appear to have a repeat-expansion in mRNA which sequesters splicing factors, thus altering the pattern of protein isoforms that are expressed.

Original languageEnglish (US)
Title of host publicationNeurodegeneration
Subtitle of host publicationThe Molecular Pathology of Dementia and Movement Disorders: Second Edition
Number of pages5
ISBN (Print)9781405196932
StatePublished - Sep 21 2011


  • Dentatorubropallidoluysian atrophy
  • Friedreich's ataxia
  • Huntington's disease
  • Spinobulbar muscular atrophy
  • Spinocerebellar ataxia


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