TRINUCLEOTIDE REPEATS IN NEUROGENETIC DISORDERS

Trinucleotide repeat expansion is increasingly recognized as a cause o f neurogenetic diseases. To date, seven diseases have been identified as expanded repeat disorders: the fragile X syndrome of mental retarda tion (both FRAXA and FRAXE loci), myotonic dystrophy, X-linked spinal and bulbar muscular atrophy, Huntington's disease, spinocerebellar ata xia type 1, dentatorubral-pallidoluysian atrophy, and Machado-Joseph d isease. All are neurologic disorders, affecting one or more regions of the neuraxis. Moreover, five of the seven (the last five above) are p rogressive neurodegenerative disorders whose strikingly similar mutati ons suggest a common mechanism of neuronal degeneration. In this artic le we discuss specific characteristics of each trinucleotide repeat di sease, review their shared clinical and genetic features, and address possible molecular mechanisms underlying the neuropathology in each di sease. Particular attention is paid to the neurodegenerative diseases, all of which are caused by CAG repeats encoding polyglutamine tracts in the disease gene protein.