Trinucleotide repeat expansion and neuropsychiatric disease

Trinucleotide, or triplet, repeats consist of 3 nucleotides consecutively r epeated (eg, CCG CCG CCG CCG CCG) within a region of DNA, a not uncommon mo tif in the genome of humans and other species. In 1991, a new type of genet ic mutation was discovered, known as a dynamic or expansion mutation, in wh ich the number of triplets in a repeat increases and the length becomes uns table. During the past decade, nearly 20 diseases-including Huntington dise ase, 2 forms of the fragile X syndrome, and myotonic dystrophy-caused by tr inucleotide repeat expansions have been identified. The unstable nature of the expanded repeat. leads to remarkable patterns of inheritance in these d iseases, distinctly at odds with traditional notions of mendelian genetics. We review the clinical and genetic features of these disorders, with a par ticular emphasis on their psychiatric manifestations, We also critically ex amine the hypothesis that expansion mutations may have an etiologic role in psychiatric diseases such as bipolar disorder, schizophrenia, and autism.