TRIPLET REPEAT GENE-SEQUENCES IN NEUROPSYCHIATRIC DISEASES

The human genome has many nucleotide repeat sequences. These range fro m a single repeating base to entire duplicated genes. Expansion of rep eating triplets of nucleotides in the genome has recently been associa ted with nine degenerative and developmental neuropsychiatric diseases : fragile X syndrome, fragile X-linked mental retardation, myotonic dy strophy, Friedreich's ataxia, spinal and bulbar muscular atrophy, Hunt ington's disease, spinocerebellar ataxia type 1, dentatorubral-pallido luysian atrophy, and Machado-Joseph disease. These diseases are all co nditions of the central nervous system; in all of them, the inheritanc e pattern usually exhibits the phenomenon of anticipation (defined as progressively earlier age of onset or a worsening disease severity ove r successive generations), and the severity of the phenotypic expressi on and penetrance appears to be related to the extent of the triplet e xpansion. identification of this pathological genetic phenomenon solve s several of the mysteries that surrounded these conditions but raises many important questions regarding pathogenic mechanisms that may be shared. There is some indication that triplet expansions may also unde rlie other neuropsychiatric conditions such as schizophrenia or bipola r disorder.