Fourteen and counting: unraveling trinucleotide repeat diseases

The pathological expansion of unstable trinucleotide repeats currently is k nown to cause 14 neurological diseases, Over the past several years, resear chers have concentrated on the challenging task of identifying the mechanis m by which the expanded trinucleotide repeat leads to abnormal cellular fun ction, As a consequence, the trinucleotide repeat field has grown dramatica lly since the initial discovery of dynamic mutations less than a decade ago . Trinucleotide repeat expansions may prove to cause pathology through a va riety of mechanisms including interference with DNA structure, transcriptio n, RNA-protein interaction and altered protein conformations/interactions. The goal of this review is to provide a brief description of the genes harb oring expanded repeats, coupled with new insights into the molecular pathwa ys most likely to be disrupted by these expansions. Data from studies of pa tient material, cell culture and animal models demonstrate the complexity o f the pathogenic mechanisms in each of the diseases.