Molecular diagnosis of neurogenetic disorders involving trinucleotide repeat expansions

Abstract

There are more than 15 known neurogenetic disorders involving trinucleotide repeat expansion. Expanded repeats range from small expansions of 20-100 copies to larger expansions of up to several thousand units. These dynamic expansions result in variability in age of onset, degree of severity and clinical presentation. Individuals carrying alleles in the intermediate range, known as premutation alleles, are often asymptomatic, but can potentially transmit a further expanded allele to his/her offspring. For autosomal dominant adult-onset disorders, carriers are asymptomatic prior to disease onset. With current molecular tools, it is now possible to determine the presence and number of expanded repeats for accurate diagnosis, presymptomatic testing and carrier status screening. This review examines some of the current approaches for molecular diagnosis and discusses the issues unique to triplet repeat diseases.