Huntington's disease.
Early in 1993, an unstable, expanded trinucleotide repeat in a novel gene of unknown function was identified on HD chromosomes. This discovery unleased a flurry of experimentation that has established the expanded CAG repeat the almost universal cause of the characteristic neurologic symptoms and pathology of this neurodegenerative disorder of midlife onset. The biochemical basis for the specific neuronal loss of HD remains uncertain, but the genetic lesion probably acts via its consequent polyglutamine segment in the protein product, huntingtin. This review will describe the basic parameters of the HD repeat's behavior and the knowledge that has accumulated concerning its potential mechanisms of action.
Gusella
J F
JF
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown 02129, USA.
MacDonald
M E
ME
D017668:Age of Onset; D000483:Alleles; D000818:Animals; D004247:DNA; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid
D004247:DNA