The third Gordon Research Conference on CAG Triplet Repeat Disorders is scheduled from July 24-29, 2005 and will take place at Mount Holyoke College in Massachusetts. This was the site of the 2001 Gordon Conference on CAG Triplet Repeats Disorders. It is an exceptionally beautiful venue that offers both perfect conditions for creative discussions and exchange of scientific ideas and results.

Triplet repeat mutations and the disorders they cause fall broadly into two groups. In the first, the expanded repeat is located in the coding region of the gene. In all but one case, the repeat is CAG, which results in an abnormally long polyglutamine tract in the mutant protein. In the second group, the triplet repeat expansion resides in a non-coding region of the gene: the 5' untranslated region in the case of Fragile X Syndrome, the 3' untranslated region in Myotonic Dystrophy and within intron 1 for Friedreich's Ataxia. This year we have included one session concentrating on expansions in non-coding regions. In the coding regions, the CAG/polyglutamine repeat diseases include Huntington's disease (HD), the spinocerebellar ataxias (SCAs) 1, 2, 3, 6, 7 and 17, spinal and bulbar muscular atrophy (SBMA) and dentatorubral pallidoluysian atrophy (DRPLA). These disorders generally have an age of onset in mid-life, although most also have juvenile forms. They all exhibit a gradual progression of symptoms that finally result in severe neurological disease. The proteins that contain these mutations are generally ubiquitously expressed and are unrelated except for the polyglutamine tract. They result in a selective loss of neurons in the brain and spinal cord, but with a different anatomical distribution for each disorder. Although the genetic defects have been established, the mechanism(s) by which the mutant protein initiates the specific pathogenic process for each disease, leading to a characteristic anatomical pattern of changes, remains to be elucidated. This conference is intended to promote understanding of molecular mechanisms operating in these diseases and ultimately assist in the development of curative treatments.