Trinucleotide repeat expansion and neuropsychiatric disease

Russell L. Margolis, Melvin G. McInnis, Adam Rosenblatt, Christopher A. Ross

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)1019-1031
Number of pages13
JournalArchives of general psychiatry
Issue number11
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health


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