Expansion of trinucleotide repeats is now recognized as a major cause of 
neurological disease. At least seven disorders result from trinucleotide repeat 
expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X 
syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, 
Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and 
dentatorubral-pallidoluysian atrophy (DRPLA). The expanded trinucleotide repeats 
are unstable, and the phenomenon of anticipation, i.e., worsening of disease 
phenotype over successive generations, correlates with increasing expansion 
size. In this review, we compare the clinical and molecular features of the 
trinucleotide repeat diseases, which may be classified into two types. Fragile X 
and myotonic dystrophy are multisystem disorders usually associated with large 
expansions of untranslated repeats, while the four neurodegenerative disorders, 
SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of 
CAG repeats within the protein coding portion of the gene. CAG repeats encode 
polyglutamine tracts. Polyglutamine tract expansion thus appears to be a common 
mechanism of inherited neurodegenerative disease. Although polyglutamine tract 
lengthening presumably has a toxic gain of function effect in the CAG 
trinucleotide repeat disorders, the basis of this neuronal toxicity remains 
unknown.